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1
Gu, Shuang. "Secretin interactions in the type II secretion system." Thesis, Queen Mary, University of London, 2012. http://qmro.qmul.ac.uk/xmlui/handle/123456789/2482.
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The type II secretion system (T2SS) is the major terminal branch of the general secretory pathway. It is composed of 12-15 proteins, most in multiple copies, and spans the inner and outer membranes of Gram-negative bacteria. The T2SS secretin subunits form a large dodecameric torus-like structure in the outer membrane. The secretin is the only essential component in the outer membrane and secreted proteins and virulence factors pass through the pore in the toroidal secretin dodecamer and out into the environment. The interaction between the secretin and its partners plays a key role in regulation of the T2SS. The interaction between the so-called homology region of the innermembrane protein GspC (GspC-HR) and secretin provides the structural and functional integrity of the secretion machinery across the two cell membranes. The interaction between secretin and its pilotin translocates the secretin subunits to the outer membrane. In this Thesis, the interactions between secretin and its partners are studied at molecular level. The GspC-HR structure is solved using NMR spectroscopy. Its interaction with secretin (GspD) is elucidated using several biochemical and biophysical approaches and a model of the complex is proposed. Also, the interaction between secretin (GspD) and pilotin (GspS) is further charicterisied. An 18 residues secretin sequence is identified as responsible for interacting with pilotin. Upon binding to the pilotin, the unstructured secretin forms a helical structure.
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Lau, Kwan-wa. "Cloning and characterization of the first amphibian secretins and secretin receptor functional implication of secretin with orexin in amphibians /." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B44143655.
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Woods, Birgitta A. "The effects of epinephrine, AVP, norepinephrine, and acetylcholine on lung liquid production in in vitro preparations of lungs from fetal guinea pigs (Cavia porcellus)." Thesis, University of British Columbia, 1991. http://hdl.handle.net/2429/29821.
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This study examined the effects of epinephrine, norepinephrine, AVP and ACh on fluid movement by the lungs of the late-term guinea pig fetus. Catecholamines and AVP are secreted in high amounts by the fetus during delivery, and could be important with respect to fetal lung fluid removal; this event is vital at the time of birth.
The lungs were supported in vitro for a duration of three hours, and production rates were measured using a dye-dilution technique. The average resting production rate in terms of ml/kg‧h declined with gestational age (54-67 days gestation; n=171). There was a lesser decline in the average resting production rate in terms of ml/h. The average production rate of untreated preparations in the first hour was 1.60 ± 0.26 ml/kg body weight per hour, and rates did not change significantly during the remaining two hours of experimentation (n=30). This rate is comparable to those reported from chronically catheterized fetal sheep.
Treatment was administered during the second hour of experimentation, following an ABA design. Lungs (n=36) were transferred to fresh Krebs-Henseleit saline containing one of the following concentrations of epinephrine: (a) 10‾⁵ M; (b) 10‾⁶ M; (c) 10‾⁷ M; (d) 5 x 10‾⁸ M; (e) 10‾⁸ M; and (f) 10‾⁹ M. With the exception of the top dose, epinephrine treatment caused an immediate reduction in fluid secretion, or fluid reabsorption. Sodium followed the movement of water in all cases. The effect of epinephrine at 10‾⁷ M was maximal, and the threshold dose for epinephrine was calculated at 1.78 x 10‾¹¹ M. Phentolamine and propranolol had no effect in control preparations. However, phentolamine completely blocked the effect of epinephrine, whereas propranolol was ineffective. Isoproterenol had no effect on pulmonary fluid production. Alpha-adrenergic receptors apparently mediate the effect of epinephrine on pulmonary fluid movement in the fetal guinea pig lung. This conclusion is different from that obtained in fetal sheep, in which beta-adrenergic receptors are utilized.
A possible synergism between epinephrine and AVP was examined. Lungs (n=12) were transferred to fresh Krebs-Henseleit saline containing either (a) 0.6 mU/ml AVP, or b) 0.6 mU/ml AVP combined with epinephrine at 10‾⁷ M. Treatment with AVP caused a slow, prolonged reduction in fluid production. Treatment with AVP together with epinephrine did not demonstrate synergism.
The effect of norepinephrine (NE) was examined. Lungs (n=36) were transferred to fresh Krebs-Henseleit saline containing one of the following concentrations of NE: (a) 1.24 x 10‾⁵ M; (b) 1.24 x 10‾⁶ M; (c) 1.24 x 10‾⁷ M; (d) 5.24 x 10‾⁸ M; (e) 1.24 x 10‾⁸ M; and (f) 1.24 x 10‾⁹ M. In all preparations, treatment with NE resulted in an immediate reduction in fluid production, and reabsorptions were observed at the higher doses. Sodium followed the movement of water in every case. The threshold dose was calculated at 3.16 x 10‾¹⁰ M. Phentolamine blocked the effect of NE, reinforcing the importance of pulmonary alpha-adrenergic receptors in the fetal guinea pig. There was no relationship between age and degree of response with treatment of either epinephrine or NE, but fetuses under 78.0 g did not respond to NE.
The effect of ACh was examined. Lungs (n=24) were transferred to fresh Krebs-Henseleit saline containing one of the following concentrations of ACh: (a) 10‾⁴ M; (b) 10‾⁵ M; (c) 10‾⁶ M; and (d) 10‾⁸ M. At the three top doses, immediate and powerful reabsorptions of pulmonary fluid were observed in older fetuses (60 days gestation and above); significant falls were observed in the younger fetuses. This result was unexpected, as it was hypothesized that ACh would stimulate fluid production. The threshold dose for ACh was between 10‾⁶ M and 10‾⁸ M. Phentolamine blocked the effect of ACh. This result suggested that reabsorption is a result of an indirect effect of ACh acting through pulmonary alpha receptors.
The results in this study show that epinephrine, NE, AVP and ACh are all important promoters of fetal pulmonary fluid removal in the fetal guinea pig. Pulmonary alpha-adrenergic receptors
mediate the effects of epinephrine, NE and ACh (indirectly). The conclusions drawn from this study emphasize the importance of species' comparison in fetal research.
LIST OF ABBREVIATIONS
AVP Arginine Vasopressin
NE Norepinephrine
DOPA dihydroxyphenylalanine
PNMT Phenylethanolamine n-methyltransferase
ACh AcetylcholineScience, Faculty of
Zoology, Department of
Graduate
4
Lau, Kwan-wa, and 劉君華. "Cloning and characterization of the first amphibian secretins and secretin receptor: functional implication ofsecretin with orexin in amphibians." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B44143655.
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Robertson, Katherine. "The role of the growth hormone/IGF-I system on islet cell growth and insulin action /." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103288.
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The study of diabetes mellitus is vital in this day and age because its incidence is increasing at an alarming rate. Diabetes results in the loss of function of beta-cells within the pancreas. Insulin resistance contributes to diabetes but the human body can compensate in various ways such as increasing the islet cell mass, glucose disposal and insulin secretion, in order to prevent the onset of diabetes. Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are two integral hormones important in both glucose homeostasis and islet cell growth. Early studies using cultured islet cells have demonstrated positive regulation of beta-cell growth by both GH and IGF-I. To evaluate their relevance on normal beta-cell growth, compensatory growth, as well as in insulin responsiveness, we have used two mouse models that represent opposite manipulations of the GH/IGF-I axis. Specifically, the growth hormone receptor gene deficient (GHR-/-) and the IGF-I overexpression (MT-IGF) mice, to help understand the role of glucose homeostasis and islet cell growth in the GH/IGF-I axis. GH is essential for somatic growth and development as well as maintaining metabolic homeostasis. It is known that GH stimulates normal islet cell growth. Moreover, GH may also participate in islet cell overgrowth and compensate for insulin resistance induced by obesity. To determine whether the islet cell overgrowth is dependent on GH signaling, we studied the response of GHR-/- mice to high-fat diet (HFD)-induced obesity. We also studied the insulin responsiveness in GHR-/- mice. On the other hand, IGF-I promotes embryonic development, postnatal growth and the maturation of various organ systems. The notion that IGF-I stimulates islet cell growth has been challenged in recent years by results from IGF-I and receptor gene targeted models. We have characterized MT-IGF mice which overexpress the IGF-I gene.The results of our studies indicate that (1) GH is essential for normal islet cell growth, but not required for compensatory overgrowth of the islets in response to obesity, (2) GHR gene deficiency caused delayed insulin responsiveness in skeletal muscle; in contrast to elevated insulin sensitivity in the liver; (3) although overexpression does not stimulate islet cell growth, a chronic IGF-I elevation caused significant hypoglycemia, hypoinsulinemia, and improved glucose tolerance, (4) finally IGF-I overexpression mice are resistant to experimental diabetes.
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Scott, Gary Terri. "The role of micro-organisms in the production of semiochemicals in the interdigital secretion of the bontebok, Damaliscus pygargus pygargus." Thesis, Stellenbosch : Stellenbosch University, 2004. http://hdl.handle.net/10019.1/53774.
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Thesis (MSc)--Stellenbosch University, 2004.ENGLISH ABSTRACT: Bontebok, Damaliscus pygargus pygargus, formerly classified as D. dorcas dorcas, are territorial animals with interdigital glands between the toes of the forelegs. Males regularly defecate on dung heaps, on which they often lie, to communicate with other members of their species. They also communicate by means of visual displays, scent marking and occasionally with scraping or pawing of dung heaps. It is assumed that scent marking with the interdigital secretion serves to define territories frequented by these antelope. These glands secrete a complex mixture of volatile and non-volatile compounds and the volatile compounds in the secretion serve as a chemical signal for other bontebok. It has been suggested that the interdigital secretion is not produced in its final composition by the interdigital gland alone, but that microbial activity is responsible for many of the compounds present in the secretion. In general, many compounds can be attributed to the by-products of microbial hydrolysis of triglycerides, a common characteristic of sebum. It is well documented that micro-organisms inhabit the deep recesses of sebaceous glands and the presence of micro-organisms has been found to be consistent in all antelope exocrine glandular areas. This study involved the chemical characterisation of the volatile metabolites produced in vitro by micro-organisms from the interdigital cavity of the bontebok. Various comparative studies were made, one of which was comparison of the metabolites produced by the individual microbial species as well as the total community of bacteria incubated in different media. A comparison of the compounds identified in the interdigital secretion and the metabolites produced by the micro-organisms in the different media was also made. The volatile metabolite extracts of the individual bacterial species and of the total community were chemically characterised by low-resolution gas chromatography-mass spectroscopy. Classes of compounds identified from the volatile metabolite extracts include: • Acids - Aliphatic (saturated and unsaturated) • Alcohols - Aliphatic (saturated and unsaturated) • Aldehydes - Aliphatic (saturated and unsaturated) • Aromatic compounds • Ketones - Aliphatic (saturated and unsaturated) • Pyrazines • Dimethyldisulphide • Squalene and cholesterol Several qualitative differences were found between the compounds identified in the volatile metabolite extracts of the micro-organisms when incubated in tryptic soy broth (TSB) and minimal salt medium (MSM). In particular, when the microbes were incubated in TSB medium a number of pyrazines were found that were not present when utilising MSM as a medium. Additional qualitative differences were found between the compounds identified in the metabolite extracts of the individual bacterial species and the total community of bacteria, when incubated in both TSB and MSM media. A comparison of the interdigital secretion and the metabolite extracts of the microbial communities incubated in TSB and MSM revealed that many compounds produced in MSM corresponded to the compounds identified in the interdigital secretion. These corresponding compounds were found to be saturated and unsaturated acids, aldehydes and squalene. Furthermore, there was only one corresponding compound in the case of TSB as medium.
AFRIKAANSE OPSOMMING: Die bontebok, Damaliscus pygargus pygargus, voorheen geklassifiseer as D. dorcas dorcas, is 'n territoriale dier met interdigitale kliere tussen die kloutjies van die voorpote. Ramme ontlas gereeld op mishope, waarop hulle dikwels lê, om met ander lede van die spesie te kommunikeer. Hulle kommunikeer ook deur middel van visuele seine, reukmerking en soms deur mishope met die voorpote te kap of te skraap. Reukmerking met die interdigitale afskeiding dien klaarblyklik om gebiede wat deur hierdie diere bewoon word, af te baken. Die interdigitale kliere skei 'n komplekse mengsel van vlugtige en nie-vlugtige verbindings af en die vlugtige verbindings dien as chemiese sein vir ander bontebokke. Die vermoede bestaan dat die interdigitale klier nie alleen verantwoordelik is vir die finale samestelling van die interdigitale afskeiding nie, maar dat mikrobiese aktiwiteit bydra tot die produksie van baie van die verbindings wat in die afskeiding aanwesig is. Sekere verbindings kan in die algemeen toegeskryf word aan die vorming van die neweprodukte van mikrobiese hidrolise van trigliseriede, 'n algemene eienskap van sebum. Dit is bekend dat die diep holtes van vetkliere 'n goeie teelaarde is vir mikroorganismes en daar is gevind dat mikroorganismes feitlik deurgaans voorkom in alle anteloop eksokriene klierareas. Hierdie studie behels die chemiese karakterisering van die vlugtige metaboliete wat in vitro deur mikroorganismes van die interdigitale klierholte van die bontebok geproduseer word. Verskeie vergelykende studies is uitgevoer waarvan een die vergelyking was van die metaboliete wat deur die individuele mikrobiese spesies sowel as die totale gemeenskap van bakterieë geproduseer word tydens inkubasie in verskillende media. Vergelyking van die verbindings wat in die interdigitale afskeiding geïdentifiseer is met die metaboliete wat in verskillende media geproduseer is, het ook deel van die studie uitgemaak. Die vlugtige metaboliet ekstrakte van die individuele bakteriese spesies en van die totale gemeenskap is chemies gekarakteriseer deur middel van laeresolusie gaschromatografie-massaspektrometrie. Die volgende groepe verbindings is onder andere in die vlugtige metaboliet ekstrakte geïdentifiseer: • Sure - Alifaties (versadig en onversadig) • Alkohole - Alifaties (versadig en onversadig) • Aldehiede - Alifaties (versadig en onversadig) • Aromatiese verbindings • Ketone - Alifaties (versadig en onversadig) • Pirasiene • Dimetieldisulfied • Skwaleen en cholesterol Verskeie kwalitatiewe verskille is gevind tussen die verbindings wat geïdentifiseer is in die vlugtige metaboliet ekstrakte van die mikroorganismes onderskeidelik in TSB medium en MSM geïnkubeer. Opvallend was byvoorbeeld die voorkoms van pirasiene in gevalle waar mikroorganismes in TSB medium geïnkubeer is, terwyl hierdie groep verbindings afwesig was wanneer MSM gebruik is. Onderlinge kwalitatiewe verskille is ook gevind tussen die verbindings wat geïdentifiseer is in die metaboliet ekstrakte van die individuele bakteriese spesies en die totale gemeenskap van bakterieë, wanneer in TSB medium sowel as in MSM geïnkubeer is. Vergelyking van die verbindings in die interdigitale afskeiding en in die metaboliet ekstrakte van die mikrobiese gemeenskappe, het getoon dat 'n aantal verbindings wat in MSM geproduseer is, ooreenstem met verbindings wat in die interdigitale afskeiding geïdentifiseer is. Daar is gevind dat hierdie verbindings versadigde en onversadigde sure en aldehiede en skwaleen is. Met TSB as medium was daar slegs een ooreenstemmende verbinding.
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LANGLOIS, ANNIK. "Contribution a l'etude de la regulation hormonale des secretions digestives chez le porc : effets du polypeptide pancreatique sur la secretion pancreatique exocrine et la secretion biliaire chez l'animal conscient." Paris 7, 1989. http://www.theses.fr/1989PA077080.
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Carroll, Kathleen. "An investigation into the molecular mechanisms regulating IgE-mediated secretion in high- and low- secreting variants of the rat basophilic leukaemia cell-line." Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298883.
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Fong, Shi-ming. "Characterization of the human secretin receptor gene /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20792906.
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Guschinskaya, Natalia. "Caractérisation moléculaire des signaux de sécrétion des protéines sécrétées par le système de sécrétion de type II de la bactérie phytopathogène Dickeya dadantii." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10085/document.
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Le système de sécrétion de type II (T2SS) assure le transport de protéines sous une forme repliée du périplasme dans le milieu extracellulaire. Ce système est largement exploité par les bactéries à Gram négatif pathogènes des plantes, des animaux et de l'homme où il permet la sécrétion de facteurs de virulence (des toxines et des enzymes lytiques). La bactérie phytopathogène Dickeya dadantii utilise le T2SS appelé Out, pour sécréter une douzaine de pectinases qui dégradent les parois des cellules végétales. Les protéines sécrétées par le T2SS n'ont pas de motif de sécrétion apparent et leur sécrétion implique plusieurs interactions transitoires avec les composants du système. La nature moléculaire de ces interactions n'est pas connue. Afin de capter ces interactions transitoires lors du processus de sécrétion, j'ai utilisé le pontage dirigé in vivo. Cette technique repose sur l'incorporation d'un analogue photoréactif d'un acide aminé (le para-benzoyl Lphénylalanine, pBpa) à la place des résidus soupçonnés de faire partie d'un site d'interaction. Le pontage est ensuite activé par une courte exposition des cellules aux UV ce qui permet la formation des complexes protéiques. Tout d'abord, cette technique a été utilisée pour introduire le pBpa dans plusieurs régions exposées à la surface d'une exoprotéine, PelI. Cette stratégie a permis de mettre en évidence qu'un élément structural, la boucle 3 du domaine Fn3 de PelI, est impliquée dans l'interaction avec la sécrétine OutD, le composant du T2SS situé dans la membrane externe, et avec le domaine PDZ d'OutC, un composant de la membrane interne. Ces résultats suggèrent que la boucle 3 fait partie d'un motif de sécrétion. Deux autres régions ont été identifiées au sein de PelI : le linker entre les deux domaines de PelI qui est impliqué dans l'interaction avec OutD et une région exposée du domaine catalytique qui interagit avec la protéine OutC. La même approche a été utilisée pour introduire le pBpa dans les deux composants du T2SS, OutC et OutD. Ces expériences ont suggéré que le domaine PDZ d'OutC interagit avec une autre exoprotéine, PelB. Cette étude, de façon complémentaire à d'autres approches, nous a permis de démontrer certains détails moléculaires essentiels de la sécrétion par le T2SSThe type II secretion system (T2SS) transports folded proteins from the periplasm through the outer membrane into the milieu. In many pathogenic Gram-negative bacteria, the T2SS secretes various virulence factors in host tissue and is directly involved in pathogenesis. The phytopathogen Dickeya dadantii secretes a dozen of pectinases through a T2SS named Out. The secreted proteins are lacking an obvious common signal and secretion is thought to involve multiple transient interactions of folded exoproteins with several T2SS components. Molecular nature of these interactions remains unknown. To address this question we used an in vivo sitespecific photo-crosslinking approach to capture such transient interactions within the functional T2SS of D. dadantii. In this technique, the photo-crosslinker para-benzoyl-L-phenylalanine, pBpa, is introduced in vivo in place of a residue of interest and UV-irradiation of living cells provokes the formation of complexes between the protein of interest and its partners. First, in a systematic approach, pBpa was introduced at several surface-exposed sites of the secreted protein PelI. This strategy permitted us to identify that one structural element, loop 3 of Fn3 domain in PelI, interacts both with the secretin, the outer membrane T2SS component, and with the PDZ domain of OutC, an inner membrane T2SS component. These results suggest that this loop 3 is a part of the secretion motif. The same approach permitted us to identify two other regions of PelI interacting with the T2SS: a linker situated between the two domains of PelI, which interacts with OutD, and an exposed region of the catalytic domain of PelI interacting with OutC. In another approach, pBpa was introduced into the T2SS components, OutC and OutD. These experiments suggested that the PDZ domain of OutC interacts with the secreted protein PelB. This study, in complement with other approaches, allowed us to uncover some important molecular features of the protein secretion by the T2SS
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方士銘 and Shi-ming Fong. "Characterization of the human secretin receptor gene." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31220800.
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Tam, Chin-pang, and 譚展鵬. "The role of secretin in regulating aldosterone synthase expression in mouse." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/197512.
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Water and salt homeostasis is tightly controlled by both central and peripheral mechanisms. Angiotensin II (ANGII) and Vasopressin (VP) have long been known to be essential in this regulatory process. Recent studies have found that secretin (SCT) can regulate water homeostasis by playing osmoregulatory functions redundant as ANGII to stimulate VP expression and release in the hypothalamus. However, the functional role of secretin in salt homeostasis, which is closely related to water homeostasis, remains unclear. This study therefore aims to investigate the modulating function of secretin in the synthesis of aldosterone, which is known to be critical in salt regulation.
Using immunohistochemical staining, expression of secretin receptor (SCTR) was detected in the zona glumerulosa of adrenal cortex. In mouse adrenal gland, real time quantitative polymerase chain reaction showed that both intraperitoneal (IP) and intracerebral ventricular (ICV) injections of SCT significantly increased aldosterone synthase (cyp11b2) expression levels. This effect was determined to be secretin-specific as it is not observed in SCTR knockout (SCTR-/-) mice. The increase of aldosterone synthase expression levels was further confirmed by Western blot analysis. In circulation, the serum level of aldosterone was also increased by ICV SCT injection, supporting the activation of aldosterone synthase by both central and peripheral SCT. Further studies showed the ICV-SCT induced aldosterone synthase can be significantly reduced by conivaptan, a VP receptor antagonist, indicating that the stimulatory effect of SCT on aldosterone synthesis is VP-related. In low sodium diet-fed mice, both SCTR and aldosterone synthase expression level were significantly increased and elevated serum SCT level was also observed. Western blot analysis also found an increase in aldosterone synthase expression in wild type mice but not in SCTR-/- controls. These results warrant the further study of the role of SCT in sodium retention.
In summary, SCT facilitates the synthesis of aldosterone through the up-regulation of aldosterone synthase. This effect can be triggered by both central and peripheral administration of SCT. The central effect of SCT on aldosterone synthesis is vasopressin-related. SCT may also participate in the sodium retention under low-salt conditions. Taken together, this study suggests a potential function of SCT in regulating body sodium homeostasis.published_or_final_version
Biological Sciences
Master
Master of Philosophy
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Pang, Ting-kai Ronald. "Role of N-linked glycosylation on the function and expression of the human secretin receptor /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20381530.
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Adogu, Azubueze Afamefuna. "Properties of insulin-secreting cell lines." Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359534.
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Sekar, Revathi. "Role of secretin in lipid homeostasis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/198810.
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Secretin, the first hormone commencing the field of endocrinology, has been studied for its pleiotropic role in the body inclusive of its neuroactive and body water homeostatic and gastrointestinal functions. Yet, the metabolic effect of secretin remains elusive and is being proposed recently for a revisit. Recent discovery from our lab showed an anorectic response for secretin, while its role in lipid homeostasis remains largely unexplored. Exerting functions such as exocrine pancreatic secretion and gastric motility inhibition, intestinal fatty acid induced release of secretin was recently shown to be mediated by CD36. Fasting related increase in plasma secretin concentration has been proposed to be involved in lipolysis but evidences regarding lipolytic actions of secretin remain contradictory. Recent report has suggested that secretin stimulates both lipolysis and lipogenesis in adipose cells. Thus, we hypothesize that secretin modulates lipid homeostasis, which was examined under two opposite, energy deficient and energy excess, conditions.
Under energy deficient/starved state, secretin level in circulation and secretin receptor level in epididymal adipose tissue were found to be upregulated. Using secretin receptor knockout (SCTR-/-) and secretin knockout (SCT-/-) mice as controls, it was found that secretin stimulated a dose- and time-dependent lipolysis in vitro and acute lipolysis in vivo. H-89, a protein kinase A (PKA) inhibitor, attenuated the lipolytic effects of secretin in vitro, while secretin induced an increase in cAMP dependent PKA activity in vivo. Using western blot analysis, secretin was found to phosphorylate hormone sensitive lipase (HSL) at serine residue 660. Additionally, immunofluorescent studies revealed that secretin stimulated translocation of HSL from cytosol to surface of lipid droplet subsequently leading to lipolysis.
Under excess energy condition, when SCTR-/- mice and its littermates SCTR+/+ mice were subjected to high fat diet (HFD) feeding for 3 months, it was found that SCTR-/- mice gained lesser weight. Nuclear magnetic resonance imaging revealed that SCTR-/- mice exhibited lower body fat content. Additionally, HFD-associated hyperleptinaemia was alleviated in SCTR-/- mice along with metabolic syndrome as they performed better in insulin and glucose tolerance tests. Continuous monitoring by indirect calorimetry revealed similar food intake, energy expenditure and locomotor activity between SCTR-/- and SCTR+/+ mice. Interestingly, intestinal fatty acid absorption, measured by a noninvasive method, was impaired in HFD-fed SCTR-/- mice. While postprandial triglyceride release was reduced in SCTR-/- mice, it also had a significant reduction in transcript and protein levels of CD36 and its downstream mediator MTTP. Secretin, when incubated with isolated enterocytes, upregulated the expression of CD36.
In summary, during starvation, secretin stimulates lipolysis through a HSL and PKA mediated pathway. When fed a HFD, SCTR-/- mice is resistant to diet induced obesity due to impaired intestinal lipid absorption. A novel short positive feedback pathway between CD36 and secretin, functioning to maximize lipid absorption, is also being proposed. Thus for the first time, two independent role of secretin in lipolysis and in intestinal lipid absorption were discovered along with their mechanistic insights. This study paves way for developing new therapeutic strategies against metabolic disorders associated with lipid metabolism.published_or_final_version
Biological Sciences
Doctoral
Doctor of Philosophy
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Lee, Pei-Chung. "Effector Secretion Control by the Pseudomonas aeruginosa Type III Secretion System." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1301596980.
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Davis, Michael A. "Jacksonian Volcano: Anti-Secretism and Secretism in 19th Century American Culture." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1378109351.
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Roma, Leticia Prates. "Mecanismos moleculares do efeito citotoxico da dexametasona em linhagens de celulas beta e ilhotas pancreaticas." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314413.
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Orientador: Kleber Luiz de Araujo e SouzaTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo:Introdução/Objetivos. A produção de espécies reativas de oxigênio (EROs) faz parte de diversos processos fisiológicos. Nos últimos anos, o aumento de EROs têm sido associado ao desenvolvimento de diversas doenças, dentre elas o Diabetes Mellitus Tipo 2. As células beta pancreáticas são notadamente mais suscetíveis ao estresse oxidativo devido a sua baixa capacidade antioxidativa, resultado da menor expressão e atividade de enzimas antioxidantes como superóxido dismutase e peroxidases. A dexametasona, um glicocorticóide sintético, tem efeitos diabetogênicos e citotóxicos em células produtoras de insulina e ilhotas pancreáticas. Entretanto, os mecanismos pelos quais a dexametasona atua sobre as células-alvo não estão bem esclarecidos. Dessa forma, nosso objetivo foi analisar se a dexametasona induz estresse oxidativo em células produtoras de insulina RINm5F e ilhotas pancreáticas. Utilizamos três modelos: 1) células RINm5F controle, que são extremamente sensíveis ao estresse oxidativo; 2) células RINm5F superexpressando a enzima catalase (RINm5F.Cat), que são resistente ao estresse oxidativo e 3) ilhotas de ratos adultos cultivadas por 72 h com dexametasona (Dexa) e ilhotas tratadas concomitantemente com dexametasona e o antioxidante N-acetilcisteína (Dexa+NAC). Resultados: Aumento na produção de EROs foi observado em células RINm5F tratadas com dexametasona. O tratamento com dexametasona aumentou a atividade/clivagem da caspase-3 e apoptose em células RINm5F após 3 dias de cultura. Expressão protéica e atividade de Cu/ZnSOD estava aumentada após o tratamento com dexametasona, enquanto que a expressão/atividade de MnSOD não foi modulada pelo corticóide. A superexpressão da catalase em linhagens de célula beta previniu todos os efeitos citotóxicos da dexametasona, inclusive a morte celular. Elevados níveis de Cu/ZnSOD podem favorecer o aumento na geração de EROs e conseqüentemente, apoptose. Da mesma forma, ilhotas tratadas com dexametasona apresentaramaumento na produção de EROs, efeito que foi revertido quando as ilhotas foram tratadas concomitantemente com dexametasona e NAC. Redução na secreção de insulina estimulada por glicose foi observada em ilhotas cultivadas com dexametasona. O tratamento com dexametasona e NAC restaurou a secreção de insulina a níveis próximos aos controles. Uma menor produção deNAD(P)H no grupo Dexa foi observado, sendo que o grupo Dexa+NAC mostrou níveis semelhantes ao grupo controle. Não ocorreram diferenças nas concentrações intracelulares de cálcio estimulado por glicose em nenhum dos grupos. A dexametasona reduziu a expressão gênica da sinaptotagmina VII, enquanto no grupo Dexa+NAC houve um aumento da expressão desse gene em ilhotas pancreáticas. Interessantemente, o tratamento com NAC diminuiu a expressão gênica da Cu/ZnSOD. Conclusões: Nossos resultados indicam que as ações da dexametasona em células produtoras de insulina e ilhotas pancreáticas são mediadas através do aumento do estresse oxidativo, sendo a Cu/ZnSOD importante nesse processo. A superexpressão da catalase e o uso do antioxidante n-acetilcisteína previnem contra os efeitos citotóxicos do glicocorticóide.
Abstract: Introduction/Aims: Reactive oxygen species (ROS) play a dual role on living organisms, being involved in many physiological processes and also being linked to the development of several pathologies, including the type 2 diabetes mellitus. Pancreatic beta cells are very sensitive to oxidative stress because of their low antioxidant capacity, wich results from their low expression and activity of antioxidant enzymes, especially peroxidases. Dexamethasone is a synthetic diabetogenic glucocorticoid that induces cytotoxic effects on pancreatic beta cells. However, the precise mechanisms of dexamethasone toxicity on target cells are not fully understood. The aim of the present study was to analyzed whether dexamethasone induces oxidative stress in insulinproducing cells and pancreatic islets. Experimental design: The experiments were performed using 3 models: 1) RINm5F control cells, extremely sensitive to oxidative stress; 2) RINm5F cells overexpressing the enzyme catalase (RINm5F.Cat), very resistant to oxidative stress and 3) rat pancreatic islets cultured for 72 h with dexamethasone (Dexa) or cultured concomitantly with dexamethasone and the antioxidant N-acetylcysteine (Dexa+NAC). Results: An increased generation of reative oxygen species (ROS) was observed in dexamethasone-treated insulinproducing cells together with an increase in caspase-3 activity and apoptosis rate. Interestingly, exposure to dexamethasone increased the cytosolic superoxide dismutase Cu/ZnSOD protein expression and activity, while the mitochondrial MnSOD isoform was not affected by the glucocorticoid. Overexpression of catalase in insulin-producing cells prevented all the cytotoxic effects of dexamethasone. Pancreatic islets cultured in the presence of dexamethasone (Dexa) for 72 h showed increased ROS production. Glucose-stimulated insulin secretion was decreased after Dexa treatment. Intracellular ROS levels were decreased and the insulin secretion capacitywas recovered by concomitant treatment with Dexa+NAC. The total insulin content and intracellular Ca+2 levels were not modulated in either Dexa or Dexa+NAC groups. There was a decrease in the NAD(P)H production rate, used as an indicator of viability, after dexamethasone treatment. Concomitant incubation with NAC returned viability to control levels. Dexamethasone also decreased SYT VII gene expression; in contrast, the Dexa+NAC group showed increased expression of SYT VII compared to controls. Surprisingly, treatment with NAC decreased the gene expression of the antioxidant enzyme, Cu/ZnSOD. Conclusions: The cytotoxic effects of dexamethasone in RINm5F insulin-producing cells and pancreatic islets are primarily ROS-mediated. High levels of expression and activity of the Cu/ZnSOD might favour the generation of ROS. The overexpression of catalase and the use of the antioxidant Nacetylcysteine counteract the cytotoxic effects of dexamethasone.
Doutorado
Fisiologia
Doutor em Biologia Funcional e Molecular
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Sågetorp, Jenny. "Cyclic AMP Oscillations in Insulin-Secreting Cells." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk cellbiologi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9563.
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Cyclic AMP is an intracellular messenger that regulates numerous processes in various types of cells. In pancreatic β-cells, cAMP potentiates the secretion of insulin by promoting Ca2+ signals and by amplifying Ca2+-triggered exocytosis. Whereas Ca2+ signals have been extensively characterized, little is known about the kinetics of cAMP signals. To enable measurements of the cAMP concentration beneath the plasma membrane ([cAMP]pm) of individual cells, a translocation biosensor was created based on fluorescent-protein-tagged subunits of protein kinase A (PKA). Evanescent wave microscopy imaging of biosensor-expressing clonal β-cells revealed that the insulinotropic hormones glucagon and GLP-1 triggered pronounced oscillations in [cAMP]pm. Simultaneous measurements of the intracellular Ca2+ concentration showed that cAMP and Ca2+ oscillations were synchronized and interdependent. [cAMP]pm oscillations were also triggered in clonal and primary mouse β-cells by an elevation of the glucose concentration from 3 to 11 mM. These oscillations were preceded and enhanced by elevations of Ca2+. However, conditions raising cytoplasmic ATP could trigger cAMP elevations also without accompanying Ca2+ changes, indicating that adenylyl cyclase activity may be directly controlled by the substrate concentration. Experiments with 3-isobutylmethylxanthine (IBMX) and various family-selective phosphodiesterase (PDE) inhibitors indicated that [cAMP]pm oscillations are generated by periodic formation of the messenger by adenylyl cyclases. PDE1 and PDE3 as well as IBMX-insensitive mechanisms shape [cAMP]pm, but no single PDE isoform was required for glucose generation of [cAMP]pm oscillations. Recordings of single-cell insulin secretion kinetics with a fluorescent biosensor that reports formation of the phospholipid PIP3 in the plasma membrane in response to autocrine insulin receptor activation showed that [cAMP]pm oscillations were paralleled by pulsatile insulin release. Whereas adenylyl cyclase inhibition suppressed both [cAMP]pm oscillations and pulsatile insulin release, elevation of [cAMP]pm enhanced secretion. Investigation of the effects of different temporal patterns of [cAMP]pm showed that brief [cAMP]pm elevation is sufficient to trigger cytoplasmic responses, whereas sustained elevation is required to induce translocation of the PKA catalytic subunit into the nucleus. In conclusion, these studies demonstrate for the first time in mammalian cells that [cAMP]pm oscillates in response to physiological stimuli. The glucose-induced [cAMP]pm oscillations are generated by periodic cAMP production mediated by interplay between ATP and Ca2+ in the sub-membrane space, and may contribute to both triggering and amplifying pathways of insulin secretion. Apart from regulating the precise kinetics of insulin exocytosis, temporal encoding of cAMP signals might constitute a basis for differential regulation of downstream cellular targets.
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McClenaghan, Neville Hugo. "Studies of novel insulin-secreting cell lines." Thesis, University of Ulster, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284850.
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Chung, Chi-kin Samuel. "The development and characterization of a gene-knockout mouse model for secretin receptor /." View the Table of Contents & Abstract, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31491121.
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Pang, Ting-kai Ronald, and 彭鼎佳. "Role of N-linked glycosylation on the function and expression of the human secretin receptor." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31221567.
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Senthil, Vijayalakshmi. "Structure, activity and relationship studies of peptide and non-peptide analogs with secretin receptor : in search of agonist and/or antagonist." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/207206.
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Class B GPCRs are emerging target in drug research. Currently these receptors serve as drug targets for several drug discovery companies and more than 50 percent of the drugs in the market targets GPCRs. Secretin receptor is found to be expressed in various tissues. Secretin regulates many bodily functions from energy to water homeostasis through both central and peripheral system. Though it holds a history of 100 years, the major drawback is its structural insights. In evidence of its integrated role in physiology as a potential target, the lookout for a novel agonist and / or antagonist for secretin receptor is initiated.
As this target is in the primary state of drug research, it is also necessary to develop the appropriate screening platforms. Due to the lack of experimental structure of secretin receptor-ligand, a 3D virtual homology model is developed using multiple template approach. Besides virtual docking, a non-radioactive FRET competitive binding assay is also developed and substantiated to enable the receptor-ligand interaction studies. Both peptide and non-peptide analogs were screened for virtual docking, in vitro binding and functional response.
For the peptide analogs, the modifications were made either in the N or C terminal portion of the peptide based on the previous findings that C-terminal portion is involved in receptor binding followed by allosteric modifications and N-terminal portion is involved in activation. These peptide analogs exhibited binding affinity in the virtual model. Paradoxically it did not exhibit in vitro binding as predicted. Along with this, the agonistic and antagonistic functional responses of these peptide analogs were also found to be negative.
SPECS natural product library of 500 non-peptide analogs were screened virtually against secretin receptor and 32 hits were identified. Of these hits glycyrrhizin’s functions were comparable to secretin was screened for receptor binding and functional response. These in vitro assays did not exert anything positive; however an IP-GTT on WT, 〖SCT〗^(-/- )and 〖SCTR〗^(-/-) mice with acute treatment of glycyrrhizin at 10 mg/kg and chronic treatment of 5 mg/kg exhibited an interesting profile with negligible effect on 〖SCT〗^(-/- )mice whereas in WT and 〖SCTR〗^(-/-) mice it displayed a better profile with improved glucose tolerance. The chronic study serum analysis on day 28 exhibited substantial reduction in blood glucose while significant increase in serum secretin and insulin levels. As glycyrrhizin promotes secretin secretion, its acute effect on blood pressure in WT mice was also analyzed at 10 mg/kg; remarkably exhibited a significant drop in blood pressure.
In summary modifications in the peptide analogs lead to instability in the receptor-ligand binding complex in the in vitro system leading to loss of binding efficiency. In case of non-peptides, though glycyrrhizin could not exhibit in vitro response, its supplementary mechanism through secretin pathway of increased secretin release is confirmed using the WT, 〖SCT〗^(-/- )and 〖SCTR〗^(-/-) mice. The hypotensive effect with an acute treatment in WT is also revealed. Discovery of this new mechanism of an old drug could broaden the research for a new class of drug, “secretin sensitizers / promoters”.published_or_final_version
Biological Sciences
Doctoral
Doctor of Philosophy
24
Zhang, Li, and 張力. "The cerebellar mechanism of secretin in modulating mouse motor coordination and motor learning behaviors." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/207477.
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Motor coordination and motor learning processes are vital for animal survival. Both functions require the participation of cerebellar Purkinje neurons, which are the integrating center as they receive both excitatory and inhibitory inputs from various neurons and send out the sole inhibitory output of cerebellar cortex. Secretin, a classical peptide hormone, has been shown previously as a retrograde factor to up-regulate GABAergic inhibitory transmission on basket-Purkinje cell synapses in rats. In behavioral perspectives, there have been studies reporting changes of motor function, anxiety level, spatial memory and social interactions after application or deprivation of secretin. Based on current knowledge, secretin is hypothesized to modulate mouse motor coordination and motor learning behaviors through its effects on Purkinje neurons.
To test this hypothesis, a Purkinje cell-specific secretin gene knockout moue model (Pur-Sct-/-) has been developed using Cre-Loxp recombination technique. Using immunohistochemical staining and in situ hybridization, secretin expression has been shown to be specifically eliminated in Purkinje neurons. Pur-Sct-/- mice had intact general motor ability and anxiety level in an open field. Neuromuscular strength of Pur-Sct-/-mice was impaired compared to wild type littermates in wire hanging test. Motor coordination ability was compromised as shown by vertical climbing and rotarod tasks. Further tests using repeated training on rotarod suggested impaired motor learning ability. All these behavioral changes have also been observed in secretin-null (Sct-/-) and secretin receptor-null (Sctr-/-) mice, suggesting that normal motor control and motor learning depend on integrity of secretin-secretin receptor axis in cerebellum.
Postnatal neural developmental study revealed later occurrence of two motor reflexes –righting and negative geotaxis –in Pur-Sct-/-juveniles. Motor deficits in rotarod tasks persisted across mice aging from month 2 to month 9 while wire hanging impairments occurred early in Pur-Sct-/-. Secretin thus may also play a role in early postnatal cerebellar development and neural protection in mature cerebellum.
To investigate the underlying mechanism, Purkinje neurons were voltage-clamped for current recording. Secretin potentiated both spontaneous and miniature inhibitory postsynaptic currents (sIPSC and mIPSC) in wild type Purkinje cells. InPur-Sct-/- and Sctr-/- mice, basal levels of sIPSC and mIPSC were significantly decreased, suggesting a role of endogenous secretin in maintaining cerebellar inhibitory transmission. The exogenous application of secretin restored IPSC in Pur-Sct-/- but not in Sctr-/- mice to comparable wild type levels, indicating the specific binding of Purkinje-derived secretin and secretin receptor underlyingthis inhibitory potentiation.
In summary, secretin released in Purkinje neurons has significant role in maintaining normal motor coordination and motor learning functions. Secretin also participates in the facilitation of inhibitory transmission on interneuron-Purkinje synapses. This inhibitory potentiation is likely to coordinate motor behaviors, although further in vivo studies are required for substantiation. This study has demonstrated the function of secretin in modulating mouse motor coordination and motor learning behaviors, and in Purkinje neuron inhibitory transmission, suggesting its potential usage in drug development against cerebellar-related motor disorders.published_or_final_version
Biological Sciences
Doctoral
Doctor of Philosophy
25
Siu, Kwan-yin. "The development and characterization of a knockout model for secretin." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B40887674.
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Ho, Po-ki. "Transcriptional regulation of the human secretin receptor gene expression." Click to view the E-thesis via HKUTO, 1999. http://sunzi.lib.hku.hk/hkuto/record/B42575230.
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Trinh, Thi Trang Nhung. "Structural studies of type IX and type II secretion systems." Thesis, Aix-Marseille, 2019. http://www.theses.fr/2019AIXM0089.
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Les protéines synthétisées et sécrétées par les bactéries jouent des rôles importants pour leur survie. Les bactéries à Gram négatif ont développé des voies de sécrétion en tant qu'armes principales pour transporter des facteurs de virulence dans l'environnement extracellulaire ou dans des cellules hôte. L'un de ces systèmes, le T9SS a été principalement étudié chez l'agent pathogène oral Porphyromonas gingivalis et chez la bactérie mobile Flavobacterium johnsoniae. Un autre complexe, le T2SS est le principal déterminant de la virulence de la bactérie Pseudomonas aeruginosa, un agent pathogène de la fibrose kystique. Dans le cadre de ma thèse, j'ai résolu la structure atomique de plusieurs composants centraux du T9SS et du T2SS. Concernant le projet T9SS, j'ai essayé de cristalliser le domaine cytoplasmique de GldL de F. johnsoniae. La co-cristallisation de GldL avec des Nbs a été réalisée sans succès. Néanmoins, les structures cristallines de deux nanobody contre GldL ont été résolues par remplacement moléculaire. De plus, j'ai également travaillé sur la protéine PG1058 de P. gingivalis. J'ai résolu sa structure par diffraction anomale à la longueur d’onde du selenium. Concernant le projet T2SS, je me suis concentré sur la partie N-terminale de XcpQ, une sous-unité de la sécrétine. J'ai résolu la structure cristalline de XcpQN012 seul et en complexe avec le nanobody vhh04 à une résolution de 2,98 Å et de 2,9 Å, respectivement. Enfin, j'ai participé à la détermination structurale de TssK, un composant de plaque de base du système de T6SS et déterminer la structure cristalline d'un nanobody contre le domaine périplasmique de PorMProteins synthesized and secreted by bacteria serve many important roles in their survival. In particular, Gram-negative bacteria have evolved secretion pathways as the main weapons for transporting virulence factors into target cells or into the extracellular environment. One of these systems, the type IX secretion system (T9SS) or the Por secretion system, has been studied mainly in the oral pathogen Porphyromonas gingivalis and the gliding bacterium Flavobacterium johnsoniae. Another complex, the type II secretion system (T2SS) is the main determinant of the virulence of Pseudomonas aeruginosa, a cystic fibrosis pathogen. In my PhD thesis, I solved the atomic structure of several core components of both T9SS and T2SS.For the T9SS project, I tried to crystallize the cytoplasmic domain of GldL from F. johnsoniae. The co-crystallization of GldL with Nbs was unsuccessfull. The crystal structures of two nanobodies against GldL were solved by molecular replacement. I also worked on the PG1058 protein of P. gingivalis. I obtained crystals of the selenomethionine-derivatized PG1058 OmpA_C-like domain that diffracted up to 1.55 Å, and solved its structure by single-wavelength anomalous diffraction. For the T2SS project, I focused on the N-terminal part of XcpQ, a subunit of the secretin. I solved the crystal structure of XcpQN012 alone and in complex with nanobody vhh04 at a resolution of 2.98 Å and 2.9 Å, respectively. In addition, I also took part in the structural determination of the base plate component TssK of the T6SS and determined the crystal structure of one nanobody (vhh19) against the periplasmic domain of PorM
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Sani, Musa. "Weapons of mass secretion the type III secretion system of Shigella flexneri /." [S.l. : Groningen : s.n. ; University Library Groningen] [Host], 2007. http://irs.ub.rug.nl/ppn/304674354.
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Gabert, Vince Morllen. "Pancreatic secretion in pigs." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/nq21570.pdf.
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Burquez-Montijo, Jose Alberto. "Studies on nectar secretion." Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235811.
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This thesis explores the dynamic patterns in the secretion, reabsorption and concentration of nectar, and their relation with microclimate, flower visitors and the innervation of the nectaries. Case studies are presented, comprising Impatiens glandulifera, Brassica napus, Fritillaria imperialis and Borago officinalis. Nectar secretion rate and nectar solute concentration are affected by the environment, and probably by the genetic composition of the plants. Significant differences in nectar secretion rate and nectar concentration are found between plants, between times of the day and between days, but not among flowers on the same plant. Correlation matrices and correlograms help us to disentangle multiple interactions. In all the species studied, the environmental factor most likely to affect nectar secretion rate seems to be the temperature of the air. Other factors also contribute to explain the variation in nectar secretion rate, among them the stand age (probably acting through the relative sink strength of the flowers), and the number of flowers and fruits per module. The supply of assimilates to the nectary is explored by experimental defoliations and deprivation of light. In both cases an immediate response is elicited, but the degree of response varies between species. Brassica napus, for example, is much less sensitive to light deprivation or total defoliation than Fritillaria imperialis. Nectar solute concentration seems to depend mainly on the relative humidity of the air. However, some evidence suggests that plant water status might affect nectar concentration. These results, obtained from field experiments, were confirmed in controlled conditions in growth chambers. Other minor factors probably play a role, but their effects are obscured by complex physiological interactions. We conclude that in a given plant the nectar secretion rate will depend mainly on its physiological age, and on variations in air temperature, while the nectar solute concentration at a given moment will be mainly the product of the short-term plant-microclimate interaction. In this context, constraints on the evolution of nectar presentation systems are considered.
31
Song, Soon Hoo. "Dynamics of insulin secretion." Thesis, University of Edinburgh, 2000. http://hdl.handle.net/1842/22645.
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I undertook four related projects that address the pattern of insulin secretion and the specific mechanisms by which b-cell positively influences these. Project one. Direct measurement of the pattern of insulin release in the portal vein (immediately downstream of the pancreas) in human subjects in the basal state and in response to glucose stimulation. Project two. Examination of the effects of acute inhibition of insulin secretion in humans with Type 2 diabetes mellitus by diazoxide on the pattern of insulin secretion. Project three. Development and validation of a method to quantify pulsatile insulin release by cultured human islets in an open loop perifusion system. Project four. Use of the system developed and validated in project 3 to test the hypothesis that transient b-cell rest in human islets induced by diazoxide (inhibiting insulin secretion by opening b cell potassium channels) prevents loss of the first phase insulin release and pulsatile insulin secretion caused by culture of the islets in glucose concentrations comparable to those seen in Type 2 diabetes mellitus. In these experiments, the following observations were made; (1) when insulin secretion was measured, in humans directly in the portal circulation, hyperglycaemia enhanced insulin secretion through the specific mechanism of amplification of the secretory burst mass while the insulin pulse frequency remained unchanged. (2) Acute partial inhibition of insulin secretion by diazoxide in patients with Type 2 diabetes mellitus did not effect the regularity of insulin secretion but did decrease the insulin clearance rate. (3) A deconvolution programme was established that was able to detect 90% of insulin pulses delivered by single human islets. (4). Using the novel islet perfusion system it was possible to show that human islets cultured at high glucose concentrations lost first phase insulin secretion and insulin pulse amplitude but these were restored in islets exposed to a transient period of b-cell rest. The overall conclusion of these studies is that the dynamics of insulin secretion are important as well as the absolute secretion rate and that the abnormalities in these dynamics may be related in part to b cell insulin stores that can be manipulated by transient b cell rest.
32
Joseph, Sabrina S. "Functional Analysis of the YopN/SycN/YscB/TyeA Complex of Yersinia pestis." Scholarly Repository, 2009. http://scholarlyrepository.miami.edu/oa_dissertations/312.
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A plasmid-encoded Type III Secretion System (T3SS) is employed by human pathogenic yersiniae to inject effector proteins, termed Yops, directly into host cells. The secretion of Yops is tightly regulated, and occurs only upon contact with a eukaryotic cell in vivo or in media devoid of calcium in vitro. A complex containing the secreted protein YopN, its heterodimeric chaperone SycN/YscB, and TyeA is required to prevent secretion of effector Yops until the appropriate secretion-triggering signals are encountered. The mechanism by which these proteins regulate the T3S process is unknown. A mutational analysis of YopN and TyeA was performed to identify regions and residues of these proteins that are required to regulate Yop secretion. Amino-acid residues of TyeA were identified that were specifically required for the interaction of TyeA with YopN, confirming that the YopN/TyeA interaction is essential for the regulation of Yop secretion. Furthermore, analysis of TyeA mutants identified a surface-exposed region that was critical for the regulation of Yop secretion, but not required for interaction with YopN. YopN residues critical for the regulation of secretion clustered within the N- and C-terminal regions of YopN that were required to interact with the SycN/YscB chaperone and TyeA, respectively. No residues critical for the regulation of secretion were identified in the central region of YopN, suggesting that this region acts primarily to maintain proper positioning of the functional N- and C-terminal regions of this complex. A novel role for the chaperone binding domain (CBD) of YopN in the regulation of Yop secretion was identified. This role was separate from its role in binding the SycN/YscB chaperone and targeting YopN for secretion. Finally, it was demonstrated that the SycN/YscB chaperone is dispensable for the regulation of secretion if the expression of both YopN and TyeA is increased, indicating that these chaperones have no direct role in the regulation of Yop secretion. These results indicate that the YopN secretion signal and SycN/YscB chaperone function to efficiently target the YopN/TyeA complex to the T3S apparatus, whereas the YopN CBD and C-terminal region of YopN complexed with TyeA mediate the block in Yop secretion.
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Lee, Tsz-on, and 李子安. "Transcriptional regulation of the human secretin gene." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B30163389.
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Ng, Sai-ming Samuel, and 吳世明. "Secretin: expression and neuroactive functionin the cerebellum." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B42576799.
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Cheng, Yuen-yee, and 鄭婉兒. "The role of secretin in appetite control." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47752956.
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Multiple gut hormones are involved in the regulation of food intake. Secretin
(SCT), a classical gut hormone, is released into the circulation from the duodenal
S-cells when acidic chyme enters the duodenum and performs the major functions
of delaying gastric emptying, stimulating fluid secretion from pancreas and liver
to optimize the digestion process. In recent years, SCT and its receptor (SCTR)
have been identified in discrete nuclei of the hypothalamus, including the
paraventricular nucleus (PVN) and the arcuate nucleus (Arc). The occurrence of
SCT and SCTR in the brain regions that are engaged in regulating body energy
homeostasis and the release pattern of SCT after meals support a functional role of
SCT in appetite control. In this study, the effect of SCT on feeding behavior was
investigated using wild-type (wt), SCT?/?, and SCT receptor-deficient (SCTR?/?)
mice. We found that both central and peripheral administration of SCT could
reduce food intake in wt but not in SCTR?/?mice. SCT induce Fos expression in
the PVN and Arc, suggesting the activation of hypothalamic feeding centers by
this peptide. Consistent with this notion, SCT was found to increase
proopiomelanocortin (POMC), but reduce agouti-related protein (AgRP)
transcripts in the Arc, and augment thyrotropin-releasing hormone (TRH) and
melanocortin-4 receptor (MC4R) mRNA expression in the PVN. In addition,
pretreatment with SHU9119, an antagonist for MC4R, abolished the anorexia
induced by SCT, suggesting that SCT may inhibit food intake via a
melanocortin-dependent pathway. Gut hormones signals the brain to modulate the
feeding behavior via the vagal afferent nerve, bloodstream or both. Here we
showed that peripheral SCT-induced anorexia was attenuated in mice with
subdiaphragmatic vagotomy, capsaicin treatment and bilateral midbrain
transections. In summary, our data identify peripheral SCT as an anorectic peptide
exerting its action via the melanocortin system and the vagal afferent contributes a
major route in mediating the inhibitory effect of peripheral SCT on food intake.
The present findings advance our understanding of the role of gut hormones in the
regulation of appetite.published_or_final_version
Biological Sciences
Doctoral
Doctor of Philosophy
36
Losada, Bohannon Liliana Cristina. "Identification and secretion of effectors from the Pseudomonas syringae type III secretion system." College Park, Md. : University of Maryland, 2004. http://hdl.handle.net/1903/1803.
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Thesis (Ph. D.) -- University of Maryland, College Park, 2004.Thesis research directed by: Molecular and Cell Biology. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Bulahan, Rhobe Justine Artates. "Characterizing potential secretion components that increase secretion of recombinant proteins in Pichia Pastoris." Scholarly Commons, 2012. https://scholarlycommons.pacific.edu/uop_etds/812.
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The methylotropic yeast Pichia pastoris has been used for many applications, particularly for its ability to produce and readily secrete heterologous proteins. Nonetheless, there are obstacles in making this useful yeast into a more efficient secretion system that readily secretes problem proteins. In the Lin-Cereghino lab, mutant strains were developed by the method of restriction enzyme mediated integration. These mutants have the ability to secrete β-galactosidase at higher levels in comparison to the wild type. This study focused on characterizing the specific mutant ah2 for its ability to secrete HRP, SLPI, and CALB lipase proteins, as well as using transmission electron microscopy to observe the effect of the pREMI-Z mutation on the morphology. Analysis of the Ah2 protein resulted in a comparative β-galactosidase secretion study, as well as a growth rate study, between the original pREMI-Z ah2 mutant and ah2 mutant cells that were transformed with pKanB-AH2 rescue construct. Lastly, a cell localization experiment was done to examine where Ah2p localizes. By these analyses, we gain a bit more understanding of the P. pastoris secretion pathway, while also outlining a procedure by which to characterize the other pREMI-Z mutants.
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Wang, Xiaohui. "Caractérisation moléculaire du système de sécrétion de type II de la bactérie phytopathogène Dickeya dadantii : études structurales et fonctionnelles sur l’interaction entre OutC et OutD." Thesis, Lyon, INSA, 2012. http://www.theses.fr/2012ISAL0010/document.
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Le système de sécrétion de type II (T2SS) est largement exploité par les bactéries à Gram négatif pour sécréter divers facteurs de virulence depuis le périplasme vers le milieu extra-cellulaire. La bactérie phytopathogène Dickeya dadanti (ex. Erwinia chrysanthemi) utilise ce système, appelé Out, pour la sécrétion de pectinases responsable de la maladie de la pourriture molle chez de nombreuses plantes. Les deux composants essentiels du système Out, la protéine de membrane interne OutC et la sécrétine OutD, formant un pore dans la membrane externe, sont impliqués dans la spécificité de sécrétion. L'interaction entre OutC et OutD pourrait assurer l’intégrité structurelle et fonctionnelle du système de sécrétion en reliant les deux membranes. Nous avons entrepris une étude structure-fonction de ces deux composants afin d’identifier et caractériser leurs sites d’interaction et de mieux comprendre leurs rôles. Nous avons appliqué une approche intégrative impliquant une analyse in vivo par cystéine-scanning et pontage disulfure, une analyse in vitro par GST pull down et une analyse structurale d’OutC et OutD et de leurs interactions par RMN. Nos résultats indiquent la présence d'au moins trois sites d'interaction entre les régions périplasmiques d’OutC et d’OutD et suggèrent que ces interactions s’établissent par un mécanisme d’addition des brins β. Nous avons démontré qu’un site situé sur le domaine HR d’OutC pouvait interagir avec deux sites distincts d’OutD suggérant un mode d’interaction alternatif. La présence d’exoprotéines et/ou des composants de membrane interne du système OutE-L-M, modifie différemment l’affinité de ces trois sites d'interaction entre OutC et OutD. Nous proposons que ces interactions alternatives entre divers sites d’OutC et OutD pourraient refléter une succession d’étapes fonctionnelles lors du processus de sécrétion. Pour étudier le mécanisme d’adressage et d’assemblage de la sécrétine OutD dans la membrane externe, nous avons exploité les interactions entre OutD et deux composants auxiliaires du T2SS, la protéine de la membrane interne OutB et la lipoprotéine de la membrane externe OutS. Nous avons montré une interaction directe entre le domaine périplasmique d’OutB et le domaine N0 d’OutD. Une analyse structure-fonction du complexe OutS-OutD a révélé que la pilotine OutS interagit fortement avec 18 résidus à l’extrémité C-terminale de la sécrétine, entraînant la structuration sous forme hélicoïdale de cette région initialement non structurée. Ce travail nous permet de mieux comprendre le mécanisme d’assemblage et de fonctionnement du système de sécrétion de type IIThe type II secretion system (T2SS) is widely exploited by Gram-negative bacteria to secrete diverse virulence factors from the periplasm into the extra-cellular milieu. The phytopathogenic bacterium Dickeya dadanti (ex. Erwinia chrysanthemi) uses this system, named Out, to secrete several cell-wall degrading enzymes that cause soft-rot disease of many plants. The two core components of the Out system, the inner membrane protein OutC and the secretin OutD, which forms a secretion pore in the outer membrane, are involved in secretion specificity. The interaction between OutC and OutD could assure the structural and functional integrity of the secretion system by connecting the two membranes. To understand structure-function relationships between these two components and characterize their interaction sites, we applied an integrative approach involving in vivo cysteine scanning and disulfide cross-linking analysis, truncation analysis of OutC and OutD combined with in vitro GST pull-down, and structural analysis of these proteins and of their interactions by NMR. Our results indicate the presence of at least three interacting sites between the periplasmic regions of OutC and OutD and suggest a β-strand addition mechanism for these interactions. We demonstrated that one site of the HR domain of OutC can interact with two distinct sites of OutD suggesting an alternative mode of their interactions. The presence of exoproteins or/and the inner membrane components of the system OutE-L-M differently alters the affinity of the three OutC-OutD interacting sites. We suggest that successive interactions between these distinct regions of OutC and OutD may have functional importance in switching the secretion machinery between different functional states. To study the mechanism of the targeting and assembly of the secretin OutD into the outer membrane, we exploited the interactions between OutD and two auxiliary proteins, i.e., the inner membrane protein OutB and the outer membrane lipoprotein OutS. We showed a direct interaction between the periplasmic domain of OutB and the N0 domain of OutD. Structure-function analysis of OutS-OutD complex shows that the pilotin OutS binds tightly to 18 residues close to the C-terminus of the secretin subunit causing this unstructured region to become helical on forming the complex. This work allows us to better understand the assembly and function mechanism of the type II secretion system
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Lam, Pak-yan Ian, and 林柏炘. "Secretin in biliary physiology: autocrine regulation on cholangiocyte proliferation and negative feedbackregulation on duodenal secretin expression via bile acids." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43572327.
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Wuttke, Anne. "Lipid Signalling Dynamics in Insulin-secreting β-cells." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk cellbiologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-198046.
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Certain membrane lipids are involved in intracellular signalling processes, among them phosphoinositides and diacylglycerol (DAG). They mediate a variety of functions, including the effects of nutrients and neurohormonal stimuli on insulin secretion from pancreatic β-cells. To ensure specificity of the signal, their concentrations are maintained under tight spatial and temporal control. Here, live-cell imaging techniques were employed to investigate spatio-temporal aspects of lipid signalling in the plasma membrane of insulin-secreting β-cells. The concentration of phosphatidylinositol 4-phosphate [PtdIns(4)P] increased after stimulation with glucose or Gq protein-coupled receptor agonists. The glucose effect was Ca2+-dependent, whereas the receptor response was mediated by isoforms of novel protein kinase C (PKC). The increases in PtdIns(4)P were paralleled by lowerings of the phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] concentration. This relationship was not caused by conversion of PtdIns(4,5)P2 to PtdIns(4)P but rather reflected independent regulation of the two lipids. Stimulation of β-cells with glucose or a high K+ concentration induced pronounced, repetitive increases in plasma-membrane DAG concentration, which were locally restricted and lasted only for a few seconds. This pattern was caused by exocytotic release of ATP, which feedback-activates purinergic P2Y1-receptors and stimulates local phospholipase C-mediated DAG generation. Despite their short durations the DAG spikes triggered local activation of PKC. Novel PKCs were recruited to the plasma membrane both after glucose and muscarinic receptor stimulation. While the glucose-induced translocation was synchronized with DAG spiking, muscarinic stimulation induced sustained elevation of the DAG concentration and stable membrane association of the kinase. Also conventional PKCs translocated to the membrane after glucose and receptor stimulation. The glucose-induced response was complex with sustained membrane association mirroring the cytoplasmic Ca2+ concentration, and superimposed brief recurring translocations caused by DAG. Interruption of the purinergic feedback loop underlying DAG spiking suppressed insulin secretion. Since the DAG spikes reflected exocytosis events, a single-cell secretion assay was established, which allowed continuous recording of secretion dynamics from many cells in parallel over extended periods of time. With this approach it was possible to demonstrate that insulin exerts negative feedback on its own release via a phosphatidylinositol 3,4,5-trisphosphate-dependent mechanism.
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Palmer, L. R. "The route taken by Wingless in secreting cells." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1447572/.
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Wingless (Wg), the major Drosophila Wnt, contributes to patterning, growth and cell survival during development. Wg is produced in a stripe at the dorsal-ventral boundary of the wing imaginal disc, a pseudostratified epithelium. Whole mount staining of permeabilised discs reveal that the Wg protein is tightly localized in the apical region of secreting cells. By contrast, extracellular Wg is barely detectable at the apical surface. Instead, extracellular Wg is mostly found at the basolateral surface of secreting, as well as surrounding, cells. These observations suggest that, in secreting cells, apically produced Wg traffics to the basolateral surface for release and gradient formation. This possibility has not been formally investigated. Nevertheless, specific regulators of Wg secretion have been identified. For example, Wntless (Wls)/Evenness interrupted (Evi) binds Wg in the ER and transports it to the plasma membrane. Without Evi, Wg accumulates within the secretory pathway. To test the transcytosis model, I have designed means of tracking Evi and Wg in secreting cells, using classical secretory and endocytic markers as guideposts. I have constructed tagged versions of Wg and Evi, which rescue wg or evi mutants when expressed at an endogenous level. In one set of experiments, I have produced a step of Wg expression and fixed discs at subsequent time points. With this approach I have determined that Wg moves from its apical production site towards the basolateral surface. This was confirmed with experiments utilising a temperature-sensitive dynamin mutant (shibirets) to control endocytosis. With this genetic tool, I have obtained data suggesting that Evi too transits through the apical surface of expressing cells before progressing basally. Unlike Wg, Evi is not released at the basolateral surface. I suggest that instead, it is recycled to replenish the secretory pathway, where it can escort more Wg to the apical surface.
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Gonelle-Gispert, Carmen. "Characterization of SNAP-25 in insulin secreting cells." Université Joseph Fourier (Grenoble), 2002. http://www.theses.fr/2002GRE10215.
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Ferreira, Rafael Marini [UNESP]. "Secretoma da bactéria fitopatogênica Xanthomonas citri subsp. citri." Universidade Estadual Paulista (UNESP), 2009. http://hdl.handle.net/11449/92688.
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O cancro cítrico está entre as principais doenças que afetam a produção de laranjas no Brasil e é causado pela bactéria fitopatogênica gram-negativa Xanthomonas citri subsp. citri (Xac). O presente trabalho teve por objetivo analisar a expressão diferencial de proteínas secretadas pela bactéria selvagem e por um mutante (02H02) assintomático, que teve a proteína HrpB4, que participa de seu sistema de secreção tipo III (SSTT) inativada, em condição de cultivo em meio rico CN e em meio XAM1 indutor de hipersensibilidade e patogenicidade (genes hrp). As proteínas secretadas em meio de cultura foram extraídas pela ação do ácido tricloroacético (TCA) e identificadas através de espectrometria de massas. Tais análises identificaram 55 proteínas diferentes secretadas em ambos os meios de cultura, tanto para Xac quanto para 02H02, de modo que 13 destas proteínas são comuns entre a Xac e seu mutante cultivados em XAM1 e 14 são exclusivas para Xac cultivada em XAM1, as quais deixaram de ser secretadas no 02H02. Proteínas relacionadas aos genes reguladores do SSTT foram detectadas em condição infectante para ambas as bactérias, demonstrando a eficácia do meio de cultura XAM1 em induzir Hrp. Foi observado que diversas proteínas secretadas pelo sistema de secreção tipo II (SSTD) em condição infectante para Xac e seu mutante possuem um papel ativo na degradação das paredes celulares do hospedeiro e podem ser reguladas por proteínas controladoras do SSTT. Fatores de sinalização difusíveis produzidos por Xac aparentemente sofreram alteração em sua secreção no mutante devido à inativação do pilus do SSTT, demonstrando a relação dessa molécula com o SSTT. A não detecção de proteínas secretadas diretamente pelo SSTT denota que as mesmas podem estar sendo secretadas no interior de vesículas lipídicas de membrana externa, assim como ocorre em Xanthomonas campestris
Citrus canker is among the major diseases which affect citrus production in Brazil and is caused by the gram-negative phytopathogenic bacterium Xanthomonas citri subsp. citri (Xac). This work aimed to analyze the differential expression of secreted proteins by the wild bacterium and by an asymptomatic mutant (02H02), lacking the type III secretion system (TTSS) protein HrpB4, in rich cultivation medium NB and in the hrp inducing medium XAM1. The proteins secreted in all culture media have been extracted by trichloroacetic acid based protocols (TCA) and identified using mass spectrometry. The analysis identified 55 different proteins secreted in both culture medium for Xac and 02H02, of which 13 are common among Xac and its mutant cultivated in XAM1 and 14 proteins are exclusively secreted by Xac cultivated in XAM1. Proteins related to the TTSS regulatory genes have been detected in infecting condition in both bacteria, showing the effectiveness of XAM1 hrp inducing medium. It has been observed that several type II secretion system’s secreted proteins showed an active role in host cell wall degradation and may be regulated by type III secretion system’s proteins in Xac and 02H02 in infecting condition. Diffusible signal factors produced by wild Xac apparently suffered an altered secretion in the mutant due the inactivation of the type three secretion system’s pilus, showing the relationship of this molecule with this secretion system. The lack of detection of proteins secreted by the TTSS denote that these proteins may be secreted in the interior of outer membrane lipid vesicles, just like it was verified in Xanthomonas campestris
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Holland, Alexandria. "Optimisation of feedstock utilisation by Geobacillus thermoglucosidasius." Thesis, University of Bath, 2017. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.723323.
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Geobacillus thermoglucosidasius (GT) is a thermophilic, ethanol-producing bacterium capable of utilising both hexose and pentose sugars for fermentation. One strategy to improve fermentation yields would be to engineer GT strains to secrete hydrolases to increase the amount of available sugars from various feedstocks. Therefore, optimised protein secretion would be vital to improve feedstock utilisation. Secretion in the related mesophile Bacillus subtilis (BS) has been well studied, and several strategies have been developed to improve secretion of heterologous proteins in BS, one such strategy being the manipulation or changing of the signal peptide. One aim is to identify any differences in the secretion machinery and signal sequences between GT and BS. Another aim is to analyse any effects of overproduction of hydrolases and to identify any bottlenecks in protein secretion in GT. Using bio-informatics tools we find that although GT is a thermophile, the signal peptides in this organism do not differ significantly from those in BS. From a shotgun mass spectrometry approach it was also observed that unlike BS, GT undergoes significant cell lysis during growth releasing cytoplasmic proteins into the extracellular milieu, which could have implications on the levels of secreted hydrolases. A model enzyme was selected and over-produced at high levels in order to stress the secretion system in GT so as to identify any bottlenecks in secretion. The results thus far indicate that the rate limiting step in secretion could be post-translocation where the enzyme is degraded by proteases in the cell wall and extracellular milieu. The addition of protease inhibitor to growth media, increases the activity and abundance of the enzyme, suggesting that proteolysis may be a major factor when over-producing secreted enzymes at high levels.
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Odes, Harold Selwyn. "Regulation of duodenal mucosal bicarbonate secretion." Thesis, University of Cape Town, 1993. http://hdl.handle.net/11427/25542.
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The present research studied the regulation of duodenal bicarbonate secretion in the anaesthetized guinea-pig, using a model that permitted the study of active transport of bicarbonate. It was determined that dibutyryl 3' ,5'-cyclic adenosine monophosphate, vasoactive intestinal polypeptide, prostaglandin E2, carbachol and theophylline are the chief agonists of duodenal bicarbonate secretion. Vasoactive intestinal polypeptide and prostaglandin E2 act directly via distinct receptors on the duodenal enterocytes, activating adenylate cyclase and protein kinase A in sequence to initiate bicarbonate secretion. In addition, there is good evidence that the inositol phospholipid and protein kinase C cascade is also involved, possibly to a lesser extent, since tetradecanoyl-phorbolacetate and prostaglandin F2a were agonists of bicarbonate secretion. Carbachol, using a m-cholinoceptor pathway, stimulates duodenal bicarbonate secretion by releasing vasoactive intestinal polypeptide. Consistent with this finding is the observation that carbachol has no receptors on duodenal enterocytes. The role of the nicotinic pathway in bicarbonate secretion, however, remains uncertain. Duodenal bicarbonate secretion can be inhibited by somatostatin and acetazolamide. Somatostatin selectively suppresses carbachol-stimulated and VIP-stimulated duodenal bicarbonate secretion, but not PGE2-stimulated bicarbonate secretion. Receptors for somatostatin coupled to adenylate cyclase could not be detected on isolated duodenal enterocytes, which strengthens the hypothesis that carbachol does not act directly on these epithelial cells, but via a second transmitter, vasoactive intestinal polypeptide. Carbonic anhydrase activity is necessary for secretion of bicarbonate, since acetazolamide-inhibition of this enzyme decreased bicarbonate secretion, both basal and stimulated by many different agonists. Carbonic anhydrase serves as a common final step in the generation of bicarbonate in duodenal enterocytes. This enzyme was located in the cytoplasm of cells in the villus as well as the crypt cells, implying that bicarbonate secretion occurs along the length of the villus and crypt. In summary, the present research has shown direct stimulation of duodenal bicarbonate secretion by vasoactive intestinal polypeptide, which participates also in themcholinergic pathway, and by prostaglandin E2. Adenylate cyclase and protein kinase A appear to be the intracellular messengers with the primary function of initiating duodenal bicarbonate secretion. However, there is convincing evidence that the inositol phospholipid and protein kinase C cascade also activates this secretion. Somatostatin selectively stops duodenal bicarbonate secretion. Carbonic anhydrase activity in the crypt and villus is required as the final common step in bicarbonate production.
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PEREZ, FRANCK. "Secretion regulee et secretion non conventionnelle : les homeoproteines comme outils et comme objets d'etudes." Paris 6, 1995. http://www.theses.fr/1995PA066693.
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Nous nous sommes d'abord attaches a developper un nouvel outil permettant l'etude, non invasive, de la secretion regulee. Nous avons tire parti des proprietes de l'homeodomaine d'antennapedia (antphd) qui a la capacite de traverser les membranes des cellules en culture par un mecanisme independant de l'endocytose classique. Nous avons fusionne a antphd les 33 acides amines carboxy-terminaux d'une petite proteine g, rab3a, impliquee dans l'exocytose regulee. Nous avons montre que la proteine de fusion ar3ac est internalisee sans degradation par des cellules en culture, validant ainsi antphd comme vecteur de peptides exogenes. Nous avons utilise ce vecteur pour etudier la fonction de rab3 dans le modele des cellules a prolactine. L'internalisation de la sequence carboxy-terminale de rab3a ainsi que celle de rab3b (et non celle de rab1 ou rab2) bloque efficacement l'exocytose regulee de ces cellules. Ceci montre que les proteines rab3 sont impliquees dans le controle de l'exocytose regulee et suggere que, malgre leur divergence, les sequences hypervariables des deux proteines rab3 interagissent avec un meme regulateur specifique. La mise en evidence de l'internalisation d'antphd a suggere un modele ou les proteines a homeodomaine pourraient, en plus de leur fonction en tant que facteurs de transcription, etre des facteurs nucleaires a action paracrine. Nous avons d'abord teste la capacite a traverser les membranes cytoplasmiques. Ajoutee dans le milieu extracellulaire, la proteine hoxa-5 est internalisee et s'accumule dans le noyau des cellules traitees. Les homeoproteines etant depourvues de peptide signal, leur eventuelle secretion ne pourrait se faire que par des voies non conventionnelles. Nos experiences de traduction in vitro et de surexpression dans des fibroblastes suggerent effectivement une interaction entre la proteine hoxa-5 et l'appareil de secretion, laissant ouverte la possibilite d'un role paracrine pour les proteines a homeodomaine
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Lam, Pak-yan Ian. "Secretin in biliary physiology autocrine regulation on cholangiocyte proliferation and negative feedback regulation on duodenal secretin expression via bile acids /." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43572327.
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Siu, Kwan-yin, and 蕭君言. "The development and characterization of a knockout model for secretin." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40887674.
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何寶琪 and Po-ki Ho. "Transcriptional regulation of the human secretin receptor gene expression." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1999. http://hub.hku.hk/bib/B42575230.
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Chan, Yuen-yee Kathy. "Functional segregation of the highly conserved basic motifs within the third endoloop of the human secretin receptor /." Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk/hkuto/record.jsp?B23621473.
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