Dissertations / Theses: 'Pancreas'

1

Laurent, Pierre. "Contribution à l'étude du pancréas annulaire." Montpellier 1, 1988. http://www.theses.fr/1988MON11275.

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2

Altman, Jean-Jacques. "Pancreas bio-artificiel." Paris 7, 1993. http://www.theses.fr/1993PA077114.

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Dans un pancreas bio-artificiel, une membrane a permeabilite selective permet sans immunosuppression la greffe de tissu insulinosecreteur qui peut assurer ses fonctions tout en etant protege du rejet. Nous avons successivement demontre avec notre technique de macroencapsulation en fibres creuses: 1. La possibilite de normalisation metabolique au long cours dans un modele de xenogreffe d'insulinome humain chez le rat diabetique streptozotocine. 2. La prevention des complications microangiopathiques. 3. La possibilite d'encapsulation de nombreux tissus endocrines. 4. L'efficacite du modele chez la souris nod diabetique auto-immune. 5. La faisabilite chez le porc diabetique. 6. Des experiences preliminaires ont pu etre realisees chez l'homme. De nombreuses ameliorations sont encore necessaires notamment au niveau de la biocompatibilite de la membrane pour que le pancreas bio-artificiel soit un traitement du diabete insulinodependant humain

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3

Mellado, Pascale. "L'ectasie mucineuse du pancréas." Montpellier 1, 1995. http://www.theses.fr/1995MON11088.

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Manibal, Véronique. "La panniculite pancréatique." Montpellier 1, 1996. http://www.theses.fr/1996MON11003.

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Martin, Denis. "Le vipome pancréatique : à propos d'un cas." Montpellier 1, 1988. http://www.theses.fr/1988MON11373.

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6

COMPAIN, MARC. "Kyste lymphoepithelial du pancreas." Amiens, 1994. http://www.theses.fr/1994AMIEM113.

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7

Coste, François. "Etude du profil sérique des androgènes dans le cancer du pancréas exocrine : à propos de 63 malades hospitalisés, de sexe masculin." Montpellier 1, 1991. http://www.theses.fr/1991MON11191.

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8

Rives, Patrick. "Le traitement chirurgical des néoplasies de la tête du pancréas par DPC." Montpellier 1, 1992. http://www.theses.fr/1992MON11017.

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9

Durand, Luc. "Les tumeurs kystiques du pancréas." Montpellier 1, 1993. http://www.theses.fr/1993MON11052.

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10

Fan, Bo-Guang. "Effects of total parenteral nutrition on the exocrine and endocrine pancreas an experimental study /." Lund : Lund University, 1997. http://catalog.hathitrust.org/api/volumes/oclc/68945114.html.

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11

Courty, Emilie. "Adaptation de fonction et de masse des cellules bêta pancréatiques dans un modèle d'insulinorésistance induite par les glucocorticoïdes." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS035.

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Les diabètes de type 1 et de type 2 sont caractérisés par une sécrétion insuffisante d’insuline et une diminution de la masse des cellules bêta. Pouvoir régénérer une masse de cellules bêta fonctionnelle est donc un enjeu thérapeutique dans le traitement du diabète. Dans cet optique, nous cherchons à identifier des facteurs et mécanismes permettant d’augmenter la masse de cellules bêta. Nous nous sommes intéressés aux mécanismes de plasticité des cellules bêta dans un contexte d’insulino résistance.Dans un modèle murin d’insulino-résistance provoquée par administration chronique de glucocorticoïdes, nous avons mis en évidence une adaptation de fonction des cellules bêta par hypersécrétion d’insuline. De manière intéressante une augmentation continue et progressive de la masse des cellules bêta par prolifération mais surtout par néogénèse de cellules bêta a pu être observée. Bien que la néogénèse de cellules bêta ait été décrite dans d’autres modèles murins comme un processus récapitulant le programme de différenciation fœtale c’est à dire dérivant de cellules canalaires marquées par l’expression de Sox9 et re-exprimant Ngn3, nos expériences de lignage endocrine ont révélé que les cellules bêta néoformées ne dérivent pas des cellules Sox9 ou Ngn3. L’invalidation du récepteur aux glucocorticoïdes (GR) dans le pancréas n’altère pas l’adaptation pancréatique par néogénèse dans notre modèle d’hypercorticisme, suggérant un effet indirect des GC sur la néogénèse de cellules bêta. Cette hypothèse a pu être confirmée par la mise en évidence de la présence dans le sérum des souris CORT d’un facteur capable de stimuler la néogénèse des cellules bêta in vitro. Enfin après déplétion totale des cellules bêta, l’administration de GC permet une restauration partielle de la masse de cellules béta par néogénèse.Nos résultats apportent la preuve d’une néogénèse active et induite de cellules bêta dans le pancréas adulte de souris insulino-résistantes. Cette adaptation pancréatique résulte d’une communication inter organe adaptative et l’identification du facteur pro-néogénique représente une piste thérapeutique pour les pathologies liées aux déficiences du pancréas endocrine
Type 1 and type 2 diabetes are characterized by an insufficient insulin secretion and a decrease of beta cell mass. Regenerate a functional beta cell mass is a therapeutic issue in the treatment of diabetes. In this context we search to identify factors and mechanisms for increasing beta cell mass. We investigated mechanisms of beta cell plasticity in a context of insulin resistance.In a mouse model of insulin resistance caused by chronic administration of glucocorticoids, we demonstrated an adaptation of beta cell function by an important increase of insulin secretion. Interestingly, a continuous and progressive increase in the mass of beta cells by proliferation but especially by neogenesis of beta cells was observed.Although beta cell neogenesis has been described in other mouse models as a process recapitulating the fetal differentiation program deriving from ductal cells labeled with Sox9 expression and re-expressing Ngn3, our endocrine lineage model revealed that neoformed beta cells do not derive from Sox9 or Ngn3 cells. Inactivation of the glucocorticoid (GR) receptor in the pancreas does not alter pancreatic adaptation by neogenesis in our model of hypercorticism, suggesting an indirect effect of GCs on beta cell neogenesis. This hypothesis could be confirmed by demonstrating the presence in the serum of CORT mice of a factor able to stimulate neogenesis of beta cells in vitro. Finally, after complete depletion of beta cells, GC administration allows a partial restoration of the beta cells mass by neogenesis.Our results provide evidence of an active and induced beta-cell neogenesis in the adult pancreas of insulin-resistant mice. This pancreatic adaptation results from an inter-organ adaptive communication and the identification of the pro-neogenic factor represents a therapeutic track for pathologies related to endocrine pancreas deficiencies

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12

Kumar, Rohan. "An ex vivo normothermic porcine pancreas physiological model : implications for pancreas and islet transplantation." Thesis, University of Leicester, 2017. http://hdl.handle.net/2381/40404.

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Introduction: The aim of the work performed for this thesis was to establish an ex vivo normothermic porcine pancreas perfusion model which is physiological and has the potential to facilitate detailed study of both its exocrine and endocrine function. The ex vivo porcine pancreas model was used to investigate the effects of machine perfusion on parameters that may be important in graft preservation and the success of whole organ pancreas and islet transplantation. A porcine islet isolation and digestion protocol was also established to enable the assessment and quantification of islet yield and viability. Methodology: During the preliminary phase of the thesis eight porcine pancreata were recovered and perfused in order to establish a reproducible experimental protocol for an ex vivo physiological pancreas model. Subsequently nine porcine pancreata were successfully recovered and normothermically perfused with autologous blood at a mean blood pressure of 50 mmHg (normotensive). Graft viability was then compared against a further four ex vivo porcine pancreata normothermically perfused at 20 mmHg (low) pressure. Serological and haematological parameters measured were: arterial and venous oxygen gas differential, routine biochemistry, glucose concentration and graft insulin responses to glucose stimulation. Exocrine function was assessed by measuring the rate of production of pancreatic juice (volume/time) and the level of serum amylase. Immunohistochemistry for cellular viability was assessed by haematoxylin and eosin staining, M30 cytoDEATH, anti-Caspase 3 antibody, and anti-ATP synthetase complex V antibody. Results: All normotensive pancreata were perfused for a median of 3 hours (range 2–4 hours) with a mean perfusion pressure of 50 mmHg and graft flow rate of 141 mL.min-1 (95% confidence intervals 122.4 to 160 mL.min-1). In comparison, all of the ‘low’ pressure models were successfully perfused for a minimum of 4 hours, with mean perfusion pressure of 20 mmHg and graft flow rate of 40 mL.min-1 (95% confidence interval 31 to 48 mL.min-1), p < 0.05. All pancreata in both the normotensive and low pressure groups demonstrated cellular viability with evidence of oxygen consumption and preserved endocrine and exocrine function. Following statistical analysis, the ‘low’ pressure perfused porcine pancreata compared favourably in important biochemical and immunohistochemistry cellular profiles, suggesting the potential for an improved method of graft preservation with improved viability. Conclusion: The physiological behaviour of this ex vivo perfused pancreas model allows the changes that occur in recovered pancreata and the potential effect they have on islet isolation, yield and whole organ viability to be studied in detail. The model also avoids use of live animals, is reproducible and mimics a “donation after circulatory death” pancreas transplant scenario. The work in this thesis demonstrated the successful application of the model to investigate the effect of machine perfusion on variables that may influence and potentially optimise both a whole organ pancreas and islets prior to transplantation.

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13

Eckoldt, Stephanie Martina. "Glycaemic control after pancreas transplantation." Thesis, University of Bristol, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.633150.

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Background: Pancreas transplantation is considered in patients with type 1 diabetes in whom usual medical management is not able to provide adequate glycaemic control or causes frequent severe episodes of hypoglycaemia. Benefits of transplantation in terms of correction of glycaemia (hyper- and hypoglycaemia) must be weighed carefully against risks associated with surgery and lifelong immunosuppression. Improved long-term graft survival would tip the risk-benefit balance in favour of transplantation. It is not clear what factors determine longterm metabolic graft function and there is currently no clinical measure to monitor graft function or identify dysfunction Methods: Glycaemic control, insulin secretion and insulin resistance was prospectively measured in patients awaiting pancreas and islet transplantation and in a cohort of pancreas transplant recipients (n=34) at 3 months after transplantation and yearly thereafter. Islet (n=2) transplant recipients were studied at 3 monthly intervals after transplantation. Results: Patients awaiting transplantation tend to be insulin sensitive. Pancreas transplantation normalises glycaemic control and restores insulin responses. Islet transplantation improves glycaemia to a lesser degree and partially restores insulin responses. Graft function appears to decline with time after transplantation with worsening glycaemia and gradual deterioration of insulin responses. A proportion of patients have clinical and sub-clinical abnormalities in glycaemic control, which may put them at risk of future decline in graft function. A fasting plasma glucose of > 5.5 mmol/L identifies patients who are at risk of future graft decline. In these patients a three-sample oral glucose tolerance test (OGTT) can confirm whether beta cell function is deteriorating. Conclusions: Although in the short term pancreas transplantation normalises glucose homeostasis, graft function declines over time. Fasting plasma glucose and OGTT are the easiest way of identifying graft dysfunction. Identification and further investigation of dysfunction may allow 'development of interventions to support graft function and prevent long-term decline.

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14

Piper, Karen. "Studies into human pancreas development." Thesis, University of Southampton, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396790.

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15

BELY, ALAIN. "Les tumeurs carcinoide du pancreas." Angers, 1988. http://www.theses.fr/1988ANGE1033.

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16

SAPPA, PHILIPPE. "Les tumeurs cystopapillaires du pancreas." Aix-Marseille 2, 1993. http://www.theses.fr/1993AIX20830.

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17

Jougon, Jacques. "La tumeur solide et papillaire du pancréas : à propos de 4 nouveaux cas." Bordeaux 2, 1989. http://www.theses.fr/1989BOR23038.

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18

Restany, Alain. "Les tumeurs endocrines du pancréas à sécrétions multiples : considérations pathogéniques et thérapeutiques." Montpellier 1, 1988. http://www.theses.fr/1988MON11263.

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19

Puel, Eric. "Bilan actuel des moyens d'exploration du pancréas." Montpellier 1, 1988. http://www.theses.fr/1988MON11285.

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20

Lau, Janet. "Hedgehog signaling in the pancreas epithelium." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2010. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3398879.

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21

MAKLOUF, MOISE. "Radiologie des tumeurs endocrines du pancreas." Lille 2, 1990. http://www.theses.fr/1990LIL2M027.

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22

MURESAN, RAT CATHERINE. "Tumeur papillaire et kystique du pancreas." Dijon, 1994. http://www.theses.fr/1994DIJOM054.

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23

Hayes, Peter C. "Glutathione S-transferases in the pancreas." Thesis, University of Edinburgh, 1993. http://hdl.handle.net/1842/19832.

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Glutathione S-transferase (GST) is an important xenobiotic metabolising enzyme which has been extensively studied in the liver. In the first part of this study immunohistochemistry was used to identify the presence and histological localisation of different GST isoenzymes in various gastrointestinal tract tissues in the human in health and disease. GSTP was found throughout the gastrointestinal and biliary tract whilst the position and quantity of other isoenzymes varied locally. Increased expression of GSTP was observed in cholangiocarcinoma and colonic adenocarcinoma, but not hepatocellular carcinoma. In the pancreas GSTP was present in ductal and centroacinar cells, whilst GSTA was present in acinar cells. GSTM was universally present in the cells of islets of Langerhan, not demonstrating genetic polymorphism. In both chronic pancreatitis and pancreatic carcinoma increased expression of GSTP was demonstrated. Using affinity chromatography and high performance liquid chromatography GSTA, P and M were purified from human pancreatic tissue. A novel GST isoenzyme, which ran on SDS/PAGE, similar to GSTP, was identified, purified and confirmed by Western blot analysis to be a GSTA. Feeding rats exclusively on raw soya flour resulted in pancreatic hypertrophy and eventually carcinoma. Serial measurements of GST activity showed only a minor reduction with short term feeding which returned to normal with chronic administration contrary to what has been proposed (Ross & Barrowman, 1987). No selective change in GST isoenzymes was identified. A dominant cytoplasmic protein, shown both enzymatically and by Western blot analysis to be α-amylase fell dramatically with short term administration recovering only marginally with chronic administration.

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24

Barrow, John. "Transcriptional control of the endocrine pancreas." Thesis, University of Aberdeen, 2005. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU487870.

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Transcription factors are vitally important to the developmental biology of all life. They also define many of the developmental stages of organs within the body. Their expression allows for the activation of developmentally important cues and signalling cascades, through activation of specific subsets of genes. When transcription factor function is disrupted, it can have serious repercussions on the development and function of organ systems. This dysfunction, in many cases, leads to the onset of diseases such as cancer and diabetes. The general objectives of this thesis were to describe the role and function of several transcription factors vitally important in the development and maintenance of the pancreas through three lines of research. Firstly, neurogenin3 (ngn3) is vitally important to the development of the islets of Langerhans. Knocking out this gene prevents mice from developing endocrine cells of the pancreas (islets of Langerhans). This thesis set out to label the ngn3 positive precursor cell population in developing mice, and characterise their phenotype. Detailed immunohistochemistry and fluorescence activated cell sorting coupled with reverse transcriptase (RT)-PCR were employed to fully characterise the EGFP positive cell population at embryonic day (E)15.5 and E l8.5. EGFP positive cells were able to be isolated at both E l5.5 and E l8.5 and were found to co-express endocrine markers both in immunohistochemical and RT-PCR based assays. Marking cells that are developmentally important to pancreas function, and being able to identify their phenotype, may provide clues to markers that could be exploited as targets for future diabetes therapies. Secondly, pancreatic duodenal homeobox-1 (PDX-1) is another critically important transcription factor in both pancreas development and in maintaining the insulin expression of the beta cells in the islets of Langerhans. Preventing PDX-1 function causes severe agenesis of the pancreas, and mutations in the gene cause one form of diabetes. This thesis describes the production of a super-activated form of the PDX-1 protein using the transactivation domain VP 16. The main objective of this work was to drive PDX-1 function in a non-beta cell. Using chromatin immunoprecipitation (ChIP) assays, the PDX-1 VP 16 protein appeared to increase the acetylation state of the insulin promoter in the mouse non-beta cell line (alpha-TCI.6), particularly through altering the acetylation state of the insulin 2 promoter. The use of the PDX-1VP16 protein could provide a potential starting point for research into driving differentiation of stem cells to a pancreatic phenotype. Finally, there are four transcription factors that are known to drive expression of the insulin gene synergistically. They are the homeodomain protein PDX-1, the leucine zipper protein MafA, and the basic helix loop helix heterodimer beta2/E47. All of these proteins have binding sites within 300 bp of the transcriptional start site of the insulin gene. Through the use of ChIP assays this thesis shows, for the first time, the ordered cyclical binding of these four transcription factors on the insulin 2 gene promoter in the mouse beta cell line MIN-6. Understanding how the transcription factors that drive insulin expression interact on the promoter in vivo could be used for future studies to understand the process of insulin gene transcription both in healthy and diabetic patients. This may then shed light on the processes that cause the perturbations in insulin transcription seen with certain forms of diabetes.

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25

GROSS, RUDOLPH. "Tumeurs kystiques du pancreas et echoendoscopie." Lyon 1, 1993. http://www.theses.fr/1993LYO1M253.

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26

GRENU, ODILE. "Les tumeurs benignes solides du pancreas : a l'exclusion des tumeurs du pancreas endocrine a propos d'un cas de fibromyome pedicule sur le pancreas chez une jeune femme." Amiens, 1988. http://www.theses.fr/1988AMIEM021.

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27

Loze, Stéphane. "La tranche pancréatique aprés exérèse partielle du pancréas : à propos de 69 cas." Bordeaux 2, 1991. http://www.theses.fr/1991BOR23047.

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28

Castera, Nathalie. "Le pseudo-kyste du pancréas : aspects diagnostiques et thérapeutiques, analyse des dossiers." Bordeaux 2, 1992. http://www.theses.fr/1992BOR23116.

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29

Ben, Othman Nouha. "Forcer la régénération des cellules bêta à l’aide des cellules alpha." Electronic Thesis or Diss., Nice, 2015. http://theses.unice.fr/2015NICE4134.

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Le diabète de type 1 (DT1) résulte de la destruction des cellules β productrices d’insuline par le système immunitaire. Cette condition représente un enjeu de santé publique majeur car, malgré les thérapies actuelles, les patients atteints développent trop souvent des complications cardio-vasculaires. Des thérapies alternatives se doivent donc d’être mises au point. Ainsi, diverses approches visent à reprogrammer/différencier (in vitro ou in vivo) différents types cellulaires pancréatiques afin de générer des cellules β (productrices d’insuline) fonctionnelles. Dans ce but, notre laboratoire a notamment montré que les cellules α (productrices de glucagon) embryonnaires peuvent être régénérées et converties en cellules β fonctionnelles par l’expression ectopique du seul gène Pax4 (un gène normalement impliqué dans la spécification embryonnaire du lignage β - (Collombat and Mansouri, 2009)). Dans la première partie de ce travail, nous démontrons que les cellules α à l’âge adulte (Al-Hasani et al., 2013) retiennent leur capacité de régénération et de conversion en cellules β, celles-ci étant fonctionnelles et capable de remplacer plusieurs fois l’ensemble des cellules β du pancréas. Cependant, cette approche transgénique serait difficile à mettre en œuvre chez l’homme. De nombreux cribles furent donc initiées dans le but de trouver des petites molécules/composés chimiques mimant les effets de Pax4. Un composé potentiel, GABA, fut ainsi identifié et caractérisé
Type 1 diabetes (T1D) results from the destruction of insulin-producing β-cells by the immune system. This condition is a major public health issue because, despite current therapies, patients often develop cardiovascular complications. Therefore alternative therapies need to be developed. Thus, various approaches are designed to reprogram / differentiate (in vitro or in vivo) different pancreatic cell types to generate functional (insulin-producing) β-cells. To this end, our laboratory has shown that especially the embryonic α-cells (producing glucagon) can be regenerated and converted into functional β-cells by the ectopic expression of the Pax4 gene (usually a gene involved in the specification of embryonic lineage β - (Collombat and Mansouri, 2009)). In the first part of this work, we show that α-cells in adulthood (Al-Hasani et al., 2013) retain their capacity for regeneration and conversion into β-cells, the latter being functional and able to replace repeatedly all the β-cells of the pancreas. However, this transgenic approach would be difficult to implement in humans. Many screens were therefore initiated in order to find small molecules / chemical compounds that mimic the effects of Pax4. A potential compound, GABA, was identified and characterized. Our results demonstrate that treatment of WT mice with GABA results in a significant increase in the number and size of the islets (caused by insulin+ cell hyperplasia). By using lineage tracing tools, our results indicate that these "β-like" neo-generated cells are coming from glucagon+ cells

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30

Chaillet, Isabelle. "Epidémiologie du cancer du pancréas." Paris 5, 1994. http://www.theses.fr/1994PA05P053.

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31

Friano, Marika Elsa. "Évaluation du rôle du facteur de transcription E2F1 dans l'identité, la fonction et la plasticité des cellules β." Electronic Thesis or Diss., Université Côte d'Azur, 2021. http://theses.univ-cotedazur.fr/2021COAZ6012.

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Selon l'Organisation mondiale de la santé, le diabète représente l'une des maladies métaboliques les plus courantes en continuelle augmentation. Le diabète est une maladie métabolique chronique qui peut être divisée en plusieurs conditions dont le diabète de type 1 et le diabète de type 2. Le diabète de type 2 (DT2) correspond à un trouble métabolique progressif causé par une résistance à l'insuline de ses tissus cibles, conduisant ainsi à une hyperglycémie et, éventuellement, à un dysfonctionnement des cellules β. Le diabète de type 1 (DT1) est le résultat d’une maladie auto-immune caractérisée par la perte progressive de cellules β productrices d'insuline. Afin de développer de nouvelles stratégies thérapeutiques dans le but d’améliorer la qualité de vie des patients diabétiques, il est important d'étudier les mécanismes moléculaires sous-tendant le développement, l'identité et la fonction des cellules β. E2F1 est un facteur de transcription impliqué dans la progression du cycle cellulaire et l'apoptose. En outre, plusieurs études ont démontré son rôle direct dans l'homéostasie du glucose et la sécrétion d'insuline. Afin de mieux comprendre le rôle de ce facteur de transcription dans les cellules β, nous avons donc généré des souris transgéniques permettant la perte constitutive ou inductible d’E2F1 dans les cellules β. De façon très intéressante, nous avons observé une intolérance au glucose chez les souris déficientes en E2F1, ainsi qu'une réduction de la masse des cellules β et une augmentation spectaculaire des populations de cellules α et δ. Nos résultats ont également montré une réduction significative des marqueurs de cellules β au niveau transcriptionel et une augmentation concomitante des marqueurs spécifiques de cellules α et δ. Toute aussi intéressante fut l’observation d’une sous-population de cellules positives pour la somatostatine exprimant des marqueurs de cellules β, des expériences de traçage de lignée confirmant une conversion des cellules β en cellules δ. De plus, l'administration d'un régime riche en graisses (HFD) révéla, qu’au regard de souris contrôles, les souris transgéniques développent bien plus rapidement une hyperglycémie causée par une altération de la sécrétion d'insuline. Ces résultats, combinés à des travaux précédents démontrant une altération de l’expression de E2F1 dans les patients DT2, suggèrent un rôle important d'E2F1 dans le maintien de l'identité et de la fonction des cellules β. Clairement, E2F1 apparait donc comme une cible moléculaire de choix dans les travaux de recherche se focalisant sur le diabète
According to The World Health Organization, diabetes represents one of the most common disease which is continuously rising. Diabetes is a chronic metabolic disease encompassing several conditions, including Type 1 and Type 2 diabetes. Type 2 diabetes (T2D) corresponds to a progressive metabolic disorder caused by an insulin resistance in target tissues, thus leading to permanent high glucose levels and eventual β-cell dysfunction. Type 1 diabetes (T1D) results from an early onset autoimmune disorder characterized by a progressive loss of pancreatic insulin-producing β-cells. In order to develop new therapeutic strategies to improve the quality of life of diabetic patients, it is important to investigate the molecular mechanisms underlying the development, the identity and the function of β-cells. E2F1 is a transcriptional factor involved in cell cycle progression and apoptosis. Besides, several studies demonstrated its direct role on glucose homeostasis and insulin secretion. In an attempt to investigate the specific role of this transcription factor specifically in β-cells, we generated transgenic mice allowing the constitutive or inducible loss of E2F1 in β-cells. Interestingly, we observed a glucose intolerance in mice lacking E2F1, together with a reduction of the β-cell mass and a dramatic enlargement of α- and δ-cell populations. Our results also indicated a significant reduction of β-cell markers at the transcript level concomitantly with an increase of both α- and δ-cell labels. Importantly, a subpopulation of somatostatin-positive cells appeared to express bona fide β-cell markers and lineage tracing experiments suggested a β-to-δ-like cell conversion. Moreover, the administration of high fat diet (HFD) revealed that, when compared to control littermates, transgenic animals were more prone to develop a hyperglycaemia as a result of impaired insulin secretion. These results, combined to previous work outlining an altered expression of E2F1 expression in T2D patients, suggest an important role of E2F1 in maintaining the β-cell identity and function, thereby opening new research avenues for diabetes research

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32

Lafitte, Marie. "Adénocarcinome canalaire pancréatique, mécanisme moléculaire et approche thérapeutique." Thesis, Bordeaux 2, 2012. http://www.theses.fr/2012BOR21941/document.

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L’adénocarcinome canalaire pancréatique est une maladie agressive et dévastatrice qui est caractérisée par une progression rapide et une résistance aux traitements. Le développement de nouveaux vecteurs à fort potentiel de transfert de gène dans les cellules tumorales pourrait être un outil performant et innovant pour améliorer les traitements existants. Nous avons développé un système de ciblage des cellules tumorales pancréatiques via l’antigène de surface Mucine 4 en utilisant des vecteurs lentiviraux spécifiques permettant le transfert efficace du gène cytotoxique de la Thymidine Kinase (hsv-TK) directement dans des modèles de tumeurs. La transduction lentivirale de cellules tumorales pancréatiques a été possible dans des xénogreffes orthotopiques. Le transfert du gène TK suivi d’un traitement au ganciclovir a montré des résultats encourageants in vivo. L’approche thérapeutique présentée ici semble être plus sécurisé, plus spécifique et aussi efficace qu’un lentivirus à large tropisme pour le transfert de gène dans les tumeurs pancréatiques. La mise en évidence de nouvelles cibles moléculaires dont la dérégulation participe au développement et à l’agressivité des tumeurs pancréatiques pourraient être utilisées pour moduler favorablement les traitements thérapeutiques en cours. De plus, ces nouvelles cibles moléculaires pourraient également servir de facteur de détection précoce ou de marqueurs pronostiques de l’adénocarcinome pancréatique. L’implication des isoformes du récepteur FGFR3 dans les mécanismes moléculaires de l’adénocarcinome pancréatique a été évaluée pour la première fois. Un rôle opposé d’oncogène et de gène suppresseur de tumeur a été découvert pour le FGFR3 en fonction du contexte cellulaire. Des voies de signalisation différentes sont empruntées pour induire ces effets opposés dans les cellules tumorales pancréatiques. Cette nouvelle donnée devra être considérée pour des thérapies ciblées impliquant des inhibiteurs de tyrosine kinases qui, s’ils sont utilisés dans un mauvais contexte cellulaire, pourraient être plus dangereux que bénéfiques
Pancreatic ductal adenocarcinoma is an aggressive and devastating disease, which is characterized by rapid progression and resistance to treatment. The development of new vectors with high potential of gene transfer in tumor cells could be an innovative and valuable tool. We have developed a strategy of pancreatic tumor cells targeting with the cell surface marker Mucin 4 using specific lentiviral vectors for the efficient transfer of the thymidine kiniase cytotoxic gene within the tumor. Lentiviral transduction of human pancreatic tumor cells was possible when cells were grafted orthotopically. The hsv-TK/GCV anti-cancer system showed promising results in vivo. The approach presented here appeared to be a safer, much more specific and an as efficient way to perform gene delivery in pancreatic tumors, in comparison with a broad tropism lentivirus. Discovering new molecular targets which modulation contributes to the development and aggressiveness of pancreatic tumors could favorably modulate the current therapies. Furthermore, these new molecular targets could also serve as factors of early detection or prognostic markers of pancreatic adenocarcinoma. The involvement of FGFR3 receptor in the molecular mechanisms of pancreatic adenocarcinoma was evaluated for the first time. Opposite roles of both oncogene and tumor suppressor gene have been discovered for FGFR3 depending on the cellular context. Importantly, molecular pathways supporting these effects are different. This new data should be considered for targeted therapies involving tyrosine kinase inhibitors. If used in the wrong cell context they could be more dangerous than beneficial

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33

Marriott, Claire. "Investigating transdifferentiation and neogenesis in the pancreas." Thesis, University of Newcastle Upon Tyne, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437940.

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Dho, Sascha Elizabeth. "Stimulation-secretion coupling in the exocrine pancreas." Thesis, University of Manchester, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233060.

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35

Shehu, Riskuwa Arabu. "Purification studies of prokallikrein from sheep pancreas." Thesis, University of Essex, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316038.

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Al-Nayel, M. Y. "Purification studies of prokallikrein from bovine pancreas." Thesis, University of Essex, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373207.

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37

LAMBLIN, PASQUIER GERALDINE. "Traitement non chirurgical des pseudokystes du pancreas." Amiens, 1988. http://www.theses.fr/1988AMIEM104.

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38

Heiser, Patrick W. "Wnt signaling in pancreas development and disease." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2007. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3261237.

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Collins, Victoria Pfoff 1945. "EFFECTS OF MANGANESE ON THE EXOCRINE PANCREAS." Thesis, The University of Arizona, 1986. http://hdl.handle.net/10150/275505.

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Seymour, Philip Allan. "Differentiation and growth of the mammalian pancreas." Thesis, University of Bath, 2003. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398416.

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Silvano, Serena. "Nouvelles stratégies de régénération et néogenèse des cellules beta pancréatiques." Electronic Thesis or Diss., Université Côte d'Azur, 2020. http://www.theses.fr/2020COAZ6035.

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Le pancréas est une glande abdominale localisée en arrière de l’estomac et connectée au duodénum, qui représente le début de l’intestin grêle. Il est constitué de deux contingents tissulaires : le compartiment exocrine, comprenant les cellules acinaires et les cellules canalaires, e le compartiment endocrine. Les cellules acinaires assurent la production d’enzymes digestives, acheminées au travers d’un réseau élaboré de canaux (formé par les cellules canalaires) jusqu’au duodénum. Le pancréas endocrine est organisé en petits groupes de cellules appelés îlots de Langerhans. Ces structures sont composées par 5 types cellulaires différents, chacune d’entre elles est dédiée à la production d’une hormone spécifique: les cellules α, β, δ, PP et ε, synthétisant respectivement les hormones glucagon, insuline, somatostatine, polypeptide pancréatique (PP) et ghréline.Notre laboratoire concentre ses recherches sur le diabète de type 1 (DT1), une maladie chronique caractérisée par la destruction auto-immune des cellules bêta, résultante en hyperglycémie chronique. Compte tenu de la complexité des mécanismes moléculaires sous-jacents au DT1 et des lacunes des thérapies actuelles, de nombreuses études sont en cours dans le but commun de trouver des approches et des thérapies alternatives à cette maladie.Dans un criblage visant à découvrir de nouveaux inducteurs de la néogenèse des cellules β, nous avons identifié deux peptides sécrétés dont l'expression et les fonctions dans le pancréas avaient été pauvrement explorées dans le passé. Après avoir établi leur profil d'expression et leur localisation dans le pancréas, nous avons recourus à des études de perte de fonction pour évaluer s'ils pouvaient jouer un rôle dans la physiopathologie du pancréas. De façon intéressante, nos données ont montré pour la première fois un rôle crucial de ces facteurs dans la régulation de la néogenèse et de la fonction des cellules β. De plus, nous avons également pu démontrer que l'administration exogène de l'un de ces deux facteurs candidats, dont la surexpression s'est avérée bénéfique pour la physiologie du pancréas par notre analyse précédente sur des modèles de souris transgéniques, était suffisante pour stimuler la prolifération des cellules β. De plus, nous avons déterminé qu'un traitement à long terme avec ce composé était capable d'augmenter considérablement la sécrétion d'insuline stimulée par le glucose, conduisant ainsi à une tolérance au glucose significativement améliorée.Ensemble, nos résultats suggèrent que ces nouveaux facteurs sécrétés jouent un rôle central sur la physiologie des cellules β pancréatiques et que les stratégies visant à contrôler leur expression pourraient être bénéfiques pour la recherche sur le diabète
The pancreas is an abdominal gland located behind the stomach and connected to the duodenum, the first portion of the small intestine. It is organized into two main tissue types: the exocrine compartment, consisting of acinar cells and a ductal system, and the endocrine tissue. Acinar cells produce digestive enzymes that are guided towards the duodenum by an organized network of ducts. The endocrine compartment is organized in highly vascularized cell clusters, termed islets of Langerhans, containing five different cell subtypes, alpha-, beta-, delta-, PP- and epsilon- cells, producing glucagon, insulin, somatostatin, pancreatic polypeptide and ghrelin hormones respectively. Our laboratory focuses its research on Type 1 Diabetes (T1D), a chronic disease characterized by the autoimmune-mediated destruction of the beta-cell pool and a consequent hyperglycemia. Given the complexity of the molecular mechanisms underlying T1D and the shortcomings of current therapies, numerous studies are undergoing with the common purpose of finding alternative approaches and therapies to this disease.In a screen seeking to uncover novel inducers of β-cell neogenesis, we identified two secreted peptides whose expression and functions in the pancreas had been poorly explored in the past. Having established their expression profile and their localization within the pancreas, we resorted to loss-of-function studies to evaluate whether they could play a role in pancreas physiopathology. Interestingly, our data showed for the first time a crucial role of these factors in regulating β-cells neogenesis and function. Additionally, we could also demonstrate that exogenous administration of one of these two candidate factors, whose overexpression was shown to be beneficial for pancreas physiology by our previous analysis on transgenic mouse models, was sufficient to stimulate β-cell proliferation. Moreover, we determined that long-term treatment with this compound was able to greatly increase glucose-stimulated insulin secretion, therefore leading to a significantly improved glucose tolerance. Together, our results suggest that these novel secreted factors play a pivotal role on pancreatic β-cell physiology and that strategies aiming at controlling their expression could be beneficial for diabetes research

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Paul, Sylvain. "Cancer anaplasique à petites cellules du poumon et du pancréas : à propos d'un cas de survie prolongée (46 mois)." Montpellier 1, 1989. http://www.theses.fr/1989MON11035.

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43

Reviron, Sophie. "Le syndrome du glucagonome : à propos d'une observation." Bordeaux 2, 1993. http://www.theses.fr/1993BOR2M018.

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Corbeil, Serge. "Réponse immunitaire humorale induite par le virus de la nécrose pancréatique infectieuse (VNPI) chez la truite mouchetée (Salvelinus fontinalis L.), et caractérisation de l'immunoglobuline produite /." Thèse, Chicoutimi : Université du Québec à Chicoutimi, 1991. http://theses.uqac.ca.

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45

Fukuda, Akihisa. "Ectopic pancreas formation in Hes1 knockout mice reveals plasticity of endodermal progenitors of the gut, bile duct, and pancreas." Kyoto University, 2007. http://hdl.handle.net/2433/135678.

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46

Thaela, Mary-Jane Sebabatso. "Biological rhythms of pancreatic secretion in young pigs with emphasis to the time around weaning /." Lund : Dept. of Animal Physiology, Lund University, 1997. http://catalog.hathitrust.org/api/volumes/oclc/39761222.html.

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Sosse-Alaoui, Anne. "Les cystadénomes du pancréas." Université Louis Pasteur (Strasbourg) (1971-2008), 1991. http://www.theses.fr/1991STR1M165.

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Halin, Lejonklou Margareta. "The MEN 1 Pancreas : Tumor Development and Haploinsufficiency." Doctoral thesis, Uppsala universitet, Endokrin tumörbiologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-175033.

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Multiple Endocrine Neoplasia Type I Syndrome (MEN 1) is a monogenic autosomal dominantly inherited cancer syndrome caused by a heterozygous loss of the MEN1 gene, predisposing for endocrine cell proliferation and tumor formation. MEN 1 carriers classically develop tumors in endocrine organs; the parathyroids, the endocrine pancreas, and the pituitary. Other organs, endocrine and non-endocrine, may also be affected. The most common cause of death in MEN 1 is pancreatic endocrine tumor (PNET), which exhibit inactivation of both MEN1 alleles. The increased proliferation prior to loss of the wild-type allele indicates haploinsufficiency, and little is known concerning the mechanisms behind MEN 1 PNET development. The MEN1 protein, menin, lacking homology with other known proteins, is involved in several aspects of transcriptional regulation and chromatin organization. We report differential expression and subcellular localization of transcription factors important in pancreatic development, in human and mouse MEN 1 pancreas, compared to non-MEN 1 pancreas. A predominantly cytoplasmic localization of Neurogenin3 and NeuroD1 was observed in tumors as well as in MEN 1 non-tumorous pancreas. Notch signaling factor expression and localization were examined in the pancreas of a heterozygous Men1 mouse model, and compared with that of wild-type littermates. Nuclear Hes1 was lost in tumors, concomitant to weaker Notch1 NICD expression, and further, analyzed using qPCR, it was shown that Notch1 was less expressed in heterozygous islets compared to wild-type islets. Performing a global gene expression array, we identified differential gene expression in five-week-old heterozygous Men1 mouse islets, compared to islets from wild-type littermates. The array results for a subset of the differentially regulated genes were corroborated using qPCR, western blotting and in situ PLA. We additionally observed significantly accelerated proliferation in islets from young heterozygous animals. It is often problematic to determine prognosis for individual patients with PNET. This is especially true in the group of patients with well differentiated endocrine carcinomas. In the absence of metastases, morphological signs of malignancy are frequently lacking. We evaluated the expression of nuclear and cytoplasmic survivin in a clinically characterized patient material (n=111), and a high nuclear survivin expression proved to be a significant negative prognostic factor for survival.

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Eeden, Susanne van. "Endocrine tumors of the pancreas and gastrointestinal tract." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2005. http://dare.uva.nl/document/78589.

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Sohrabi, Soroush. "Studies of Pancreas Viability and Function for Transplantation." Thesis, University of Sunderland, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.531442.

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Dissertations / Theses on the topic 'Pancreas'

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