Dissertationen zum Thema „Résistance au diabète“
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Riant, Elodie. „Effets protecteurs des œstrogènes sur l'insulino-résistance et le diabète de type 2“. Toulouse 3, 2009. http://thesesups.ups-tlse.fr/686/.
Der volle Inhalt der QuelleAlthought corroborating data indicate that estrogens protect against insulino-resistance and glucose metabolism throught the activation of the estrogen receptor a (ERa), it has not been established wether this pathway could represent an effective therapeutic target to fight against metabolic disturbances induced by a high-fat diet. Based on the study of animal models in vivo, our experimental approach allowed us to demonstrate that: 1) Activation of the path of ERa in vivo exerts a protective effect in a mouse model subjected to a fat diet, and more precisely, limits the development of adipose tissue, preserves insulin sensitivity of peripheral tissues and prevents also the occurrence of fasting hyperglycemia and glucose intolerance. 2) Furthermore, activation of ERa enhanced inflammatory response characterized by cytokine production in organs sensitive to insulin (liver, fat) and infiltration of macrophages in adipose tissue. This proinflammatory effect results from direct activation of cells derived from bone marrow, but appears dissociated from the metabolic protective effect. Despite its pro-inflammatory effect, selective activation of the path of ERa could be an effective strategy to reduce the deleterious impact of dietary patterns hyperlipidaemia
Hamlat, Nadjiba. „Lipogénèse de la paroi artérielle : régulation de son expression et anomalies dans l'insulino-résistance et le diabète“. Electronic Thesis or Diss., Lyon 1, 2010. http://www.theses.fr/2010LYO10071.
Der volle Inhalt der QuelleWe investigated the expression and regulation of lipogenesis in aortas and VSMC and determined if it is modified during metabolic abnormalities. Zucker obese (ZO), diabetic (ZDF) rats, and the high fat diet fed Psammomys obesus accumulated more triglycerides in their aortas than control rats. However the expression of lipogenic genes, or of genes involved in fatty acids uptake, was not increased. Lipogenesis was not increased in human carotid endarterectomy of diabetic compared to non-diabetic patients. The adipogenic medium (ADM), glucose or insulin stimulated moderately lipogenesis but only in VSMC from control rats. No effect was observed in VSMC from ZO. We showed that the lipogenic effects of TO901317observed in VSMC from Zucker control rats are due solely to the nuclear receptor LXRα, PXR agonist had no effect. Conclusion: Lipogenesis is not increased in arterial wall during insulin-resistance and diabetes
Napolitano, Tiziana. „Confidentiel“. Thesis, Université Côte d'Azur (ComUE), 2017. http://www.theses.fr/2017AZUR4141.
Der volle Inhalt der QuelleLacquemant, Corinne. „Étude génétique de l'insulino-résistance, du diabète et de leurs complications cardio-vasculaires“. Lille 1, 2000. https://pepite-depot.univ-lille.fr/LIBRE/Th_Num/2000/50376-2000-322-323.pdf.
Der volle Inhalt der QuellePar contre, l'incidence des maladies athérosclereuses prématurées a considérablement augmenté ces dernières années a l'île Maurice. Les facteurs de risque généralement associés à cette pathologie sont les anomalies du métabolisme du glucose, des lipides et des facteurs de la coagulation, l'hyperinsulinisme, l'obésité centrale et l'hypertension artérielle. Ce syndrome d'insulinorésistance à une forte composante héréditaire en raison de l'existence d'une forte prévalence de diabète et de maladie coronarienne. L'analyse familiale de liaison dans la population mauricienne nous a permis de détecter des régions liées aux différents facteurs de l'insulinorésistance. D'autres étapes seront nécessaires pour identifier et valider les gènes de prédisposition au développement de ces différentes pathologies
Duquenne, Manon. „Les tanycytes véhiculent la leptine dans le cerveau métabolique : mécanismes moléculaires et rôle dans la physiopathologie de la résistance hormonale et l'obésité/diabète“. Thesis, Lille, 2019. https://pepite-depot.univ-lille.fr/RESTREINT/EDBSL/2019/2019LILUS054.pdf.
Der volle Inhalt der QuelleThe control of energy balance that allows for the maintenance of body mass requires a continued dialogue between the periphery and the hypothalamus in the brain. The access of peripheral hormones to that structure is essential to the proper functioning of neural circuits that regulate energy balance. However, little is known about the transport mechanisms of circulating metabolic signals into the hypothalamus. The median eminence, a hypothalamic structure forming the floor of the 3rd ventricle, contains specialized ependymoglial cells called tanycytes. Tanycytes have been shown to shuttle metabolic signals such as leptin into the cerebrospinal fluid, via transcytosis. Identifying the molecular mechanisms involved in this transport is essential to our understanding of the phenomenon of central hormone resistance found in obese and type 2 diabetes patients. During my thesis, after an infusion of a recombinant fusion protein (TAT-Cre) into the 3rd ventricle of leptin receptor gene-floxed mouse model (LepR(loxP/loxP)), we investigated the role of the LepR in tanycytes on the central control of energy homeostasis in mice. Our results show that selectively impairing LepR expression in tanycytes increases body weight, adiposity, cholesterolemia, triglyceridemia and decreases noradrenaline serum concentration. It’s associated with an increase of food intake, peripheral but not central leptin anorectic effect and glucose intolerance. Pancreas and adipose tissue activity of our model is also affected. In parallel, we studied the mechanisms underlying the anorexigenic action of endozepines. Our results show that endozepines induce ERK activation necessary for leptin transport into the brain in primary culture of tanycytes and require tanycytic LepR expression to promote STAT3 phosphorylation in the hypothalamus. Finally, we also investigated the effect of the expression of the type B botulinum neurotoxin BoNTB, in tanycytes on the central control of energy homeostasis in mice. BoNTB inactivates synaptobrevins 1-3 by proteolytic cleavage and thus alters synaptobrevin-mediated exocytosis. Our results show that selectively impairing synaptobrevin function in tanycytes affects as in the previous model the basal food intake, leptin sensitivity and glucose tolerance in mice. However, we noticed some differences in pancreas activity compared to the model in which we selectively impaired LepR expression in tanycytes. Altogether, these data demonstrate for the first time the key role of tanycytes in the central control of energy regulation in-vivo and the involvement of LepR expression in tanycytes for circulating leptin and endozepines action in the metabolic brain
Hamlat, Nadjiba. „Lipogénèse de la paroi artérielle : régulation de son expression et anomalies dans l'insulino-résistance et le diabète“. Thesis, Lyon 1, 2010. http://www.theses.fr/2010LYO10071.
Der volle Inhalt der QuelleWe investigated the expression and regulation of lipogenesis in aortas and VSMC and determined if it is modified during metabolic abnormalities. Zucker obese (ZO), diabetic (ZDF) rats, and the high fat diet fed Psammomys obesus accumulated more triglycerides in their aortas than control rats. However the expression of lipogenic genes, or of genes involved in fatty acids uptake, was not increased. Lipogenesis was not increased in human carotid endarterectomy of diabetic compared to non-diabetic patients. The adipogenic medium (ADM), glucose or insulin stimulated moderately lipogenesis but only in VSMC from control rats. No effect was observed in VSMC from ZO. We showed that the lipogenic effects of TO901317observed in VSMC from Zucker control rats are due solely to the nuclear receptor LXRα, PXR agonist had no effect. Conclusion: Lipogenesis is not increased in arterial wall during insulin-resistance and diabetes
Napolitano, Tiziana. „Gfi1 : une nouvelle cible pour la thérapie du diabète“. Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2017. http://www.theses.fr/2017AZUR4141.
Der volle Inhalt der QuelleThe mature pancreas consists of two main tissue types: the exocrine tissue, including acinar cells and a ductal tree, and the endocrine tissue. Acinar cells are dedicated to the synthesis of digestive enzymes, which are collected and conveyed to the duodenum by a ductal network running through the entire organ. Endocrine cells are organized into highly vascularized cell clusters, termed islets of Langerhans, which contain five cell subtypes, α-, β-, δ-, PP- and ε-cells secreting glucagon, insulin, somatostatin, pancreatic polypeptide and ghrelin, respectively. Classical genetic approaches have revealed much about individual factors regulating pancreatic development, however, we have yet to understand the regulatory network underlying pancreas formation and all the factors involved. Some of these factors are well known and studied but increasing researches revealed new and unknown factors involved in pancreas development and maturation. Among these, through in silico studies, we accumulated evidences suggesting a role of Gfi1 in pancreas cell development and specification. This protein, a zinc finger transcription factor, had previously been implicated in hematopoiesis, inner ear cell development, and in the maintenance of intestinal cell phenotypes. Here, we investigated the role of Gfi1 in the pancreas. Towards this goal, we generated a transgenic mouse line allowing Gfi1 inactivation exclusively in the pancreas. Altogether, our observations suggest that Gfi1 is required for the full maturation of pancreatic acinar cells. Importantly, we demonstrated that the sole loss of Gfi1 in the pancreas is sufficient to protect mice against two models of diabetes induction
Lacroix, Marilyn. „Implication de l'adiponectine dans la physiopathologie du diabète gestationnel“. Mémoire, Université de Sherbrooke, 2013. http://hdl.handle.net/11143/6321.
Der volle Inhalt der QuelleMunkonda, Mercedes Nancy. „Le rôle de l'ASP dans la résistance à l'insuline et le diabète de type 2“. Thesis, Université Laval, 2012. http://www.theses.ulaval.ca/2012/29282/29282.pdf.
Der volle Inhalt der QuelleDray, Cédric. „Rôle et régulation de l'Apeline au cours de la résistance à l'insuline associée à l'obésité“. Toulouse 3, 2009. http://thesesups.ups-tlse.fr/552/.
Der volle Inhalt der QuelleApeline is a peptide synthesized by adipocytes and present in plasma under different forms such as 36, 17 and 13 aminoacids forms. During this doctoral, I have studied the apelin regulation and role during insulin resistance and type II diabetes. At first, we showed that TNFalpha, an inflammatory cytokine involved in insulin resistance, increased adipocyte apelin expression and secretion in mouse and human. Another study allows us to show a wide-range expression of apelin and APJ during type II diabetes development stages. In mouse and human, adipose tissue apelin and APJ expression is insulin sensible during insulin resistance but fails to be sensible during type II diabetes. In striated skeletal muscle, this kind of regulation is not clear and has to be more studied. At the same time, we also considered the metabolic role of apelin in mouse model. Ex vivo and in vivo experiences realised in mouse highlighted that apelin increased glucose uptake in muscle and adipose tissue. Furthermore, apelin-induced signalling pathways studies in isolated soleus muscle showed AMPK, eNOS and Akt activation. Interestingly, in high fat diet induced obese and insulin-resistant mice, we showed that apelin effect was still effective to ameliorate glucose tolerance (OGTT) and, as observed in healthy mouse, increased skeletal muscle and white adipose tissue glucose utilization. Surprisingly, glucose utilization was also increased in hearts of apelin-infused mice. Even if supplemental data are necessary, apelin seems to behave as a new anti-diabetic hormone and could be considered as a new potential target to fight metabolic diseases
Richard, Sylvie. „Syndrome d'alström et insulino-résistance : à propos de deux familles“. Lille 2, 1995. http://www.theses.fr/1995LIL2M102.
Der volle Inhalt der QuelleAttané, Camille. „Apeline et métabolisme énergétique : implication dans la résistance à l'insuline“. Toulouse 3, 2010. http://thesesups.ups-tlse.fr/1284/.
Der volle Inhalt der QuelleApelin is the endogenous ligand of the G protein-coupled receptor named APJ. Several isoforms of this peptide exists as apelin-36 and apelin-13. Apelin and APJ are expressed in the central nervous system, particularly in the hypothalamus and in many peripheral tissues (heart, lungs, endothelial cells, skeletal muscle. . . ). Apelin is involved in fluid homeostasis by its diuretic effect, in the regulation of cardiovascular function, food intake, cell proliferation and angiogenesis. Apelin has been described by our group as being produced and secreted by adipocytes in mice and humans. With obesity and associated diseases such as diabetes type 2, plasma concentrations of apelin are increased. The relationship between apelin and metabolic disorders is a new area of investigation. Recent data from our laboratory and by other teams have shown an important role of apelin on carbohydrate metabolism. The aim of the work, done during the thesis, was to study the effects of apelin on lipid metabolism on both adipose tissue and skeletal muscle in physiological and pathological conditions such as insulin resistance. First, acute effect of apelin was studied on human adipose tissue. We have shown that on adipose tissue explants, apelin stimulated AMPK, an enzyme important in regulating energy metabolism. Moreover, apelin stimulated glucose transport by an AMPK-dependent pathway but has no effect on lipolysis (basal or stimulated). Secondly, the effect of chronic apelin treatment has been studied on lipid metabolism in skeletal muscle of obese and insulin resistant mice. We have shown an increased utilization of lipids in vivo and ex vivo in the soleus muscle of mice treated with apelin. This effect was associated with increased mitochondrial biogenesis allowing better oxidative capacity of skeletal muscle. Finally, chronic treatment with apelin improves overall insulin sensitivity but also in muscle, by decreasing acylcarnitine levels and increasing insulin-stimulated glucose transport. Altogether, these results show that apelin treatment allows muscle mitochondria to better cope with a high fat diet in order to induce metabolic benefits. Since mitochondrial dysfunction is now considered as a central event in whole body metabolic dysregulation with regards to type 2 diabetes, apelin represents an attractive therapeutic target by acting on both glucose and lipid metabolism
Guillemette, Laetitia. „Implication du TNFα dans la résistance à l’insuline pendant la grossesse“. Mémoire, Université de Sherbrooke, 2015. http://hdl.handle.net/11143/6009.
Der volle Inhalt der QuelleAït, El Mkadem Samira. „Déterminisme génétique de la résistance à l'insuline : identification de défauts moléculaires dans le syndrome des ovaires polykistiques, l'obésité et le diabète sucré“. Saint-Etienne, 2000. http://www.theses.fr/2000STET004T.
Der volle Inhalt der QuelleLaurens, Claire. „De la gouttelette lipidique aux adipocytes intramusculaires : vers un lien causal avec l'insulino-résistance ?“ Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30388/document.
Der volle Inhalt der QuelleMy PhD research work was focused on the role of muscle lipids in the regulation of energy metabolism and insulin sensitivity. Lipids can be found under two different forms in skeletal muscle: adipocytes located between muscle fibers/bundles and lipid droplets inside muscle fibers (i.e. intramyocellular triacylglycerols or IMTG). These depots, when present in excess, have both been associated with insulin-resistance in humans, mainly because of intracellular lipotoxic lipid accumulation known to impair insulin signaling for IMTG, and through a yet unknown mechanism for adipocytes. First, we isolated and characterized two distinct populations of progenitor cells from human muscle biopsies. The first population is composed of satellite cells (muscle progenitor cells) and display a myogenic differentiation potential in vitro. The second population is composed of cells that acquire the phenotypic and metabolic properties of functional white adipocytes, called fibro/adipogenic progenitors (FAPs). By using these cell models, we showed that FAPs-derived adipocytes secretions are able to impair insulin signaling and action in human skeletal muscle fibers in vitro. This paracrine effect could explain, at least partly, the inverse relationship observed between intramuscular adipocyte content and insulin sensitivity in humans. Secondly, we studied the role of two proteins, G0/G1 Switch Gene 2 (G0S2) and perilipin 5 (PLIN5), in lipid droplets dynamics as well as their impact on lipid metabolism and insulin sensitivity. We showed in vitro that these two proteins play a key role in the control of muscle lipolysis (i.e. IMTG hydrolysis) via the adipose triglyceride lipase (ATGL, catalyzing the limiting step of muscle lipolysis), and that G0S2 and PLIN5 inhibit ATGL activity through direct and indirect mechanisms, respectively. Furthermore, our data showed that G0S2 and PLIN5 invalidation in vivo in mouse skeletal muscle activates lipolysis, increases lipotoxicity and impairs insulin sensitivity. We have also highlighted an important role for PLIN5 in the regulation of fatty acids oxidation, by finely adjusting their availability to energy demand. Overall, these results clearly show on one hand that a crosstalk between adipocytes and fibers within skeletal muscle can lead to an alteration of insulin sensitivity in humans, and on the other hand that G0S2 and PLIN5, two lipid droplet proteins, play a central role in the control of muscle lipid homeostasis and insulin sensitivity. These data help to develop our current understanding of the link between muscle lipids and insulin sensitivity in humans
André, Philippe. „Marqueurs hépatiques , syndrome métabolique d'insulino-résistance et diabète de type 2 : analyse des liens entre marqueurs hépatiques, anomalies du syndrome métabolique d'insulino-résistance et métabolisme des hydrates de carbone“. Paris 11, 2007. http://www.theses.fr/2007PA11T062.
Der volle Inhalt der QuelleSimoni, Yannick. „L’immunité innée dans le diabète sucré“. Thesis, Paris 5, 2013. http://www.theses.fr/2013PA05T074/document.
Der volle Inhalt der QuelleThe type 1 diabetes ( T1D ) is an autoimmune disease characterized by the destruction of β cells in the pancreas by autoreactive T lymphocytes. During my thesis, we are interested in the role of cells of innate immunity in T1D using a mouse model of the disease: NOD mice. In contrast to cells of the adaptive system (T and B lymphocytes ) cells of innate immunity is the first line of defense of the body during infection . This population consists of neutrophils , among other , plasmacytoid dendritic cells ( pDC ) , macrophages , T lymphocytes but not conventional B as iNKT cells and B -1a.Previously, our laboratory has highlighted the role of iNKT cells in the development of T1D . During the first part of my thesis , we demonstrated that iNKT17 cells, a subpopulation of iNKT cells, have a deleterious role in T1D in NOD mice . These cells infiltrate the pancreas and there produce IL -17 , a proinflammatory cytokine. Through transfer experiments , we demonstrated that lymphocytes iNKT17 exacerbate disease through the production of IL-17 . In the second part of my thesis , we investigated the mechanisms that induce the activation of autoreactive T lymphocytes. We observed in NOD mice , the physiological death of β cells leads to activation of innate immunity cells : neutrophils, lymphocytes B- 1a and pDCs . The cooperation between these cells leads to activation of pDC that produce IFNa . This cytokine activates autoreactive T cells which will destroy the β cells of the pancreas. Our results show that innate immunity is an important player in the pathogenesis of diabetes mellitus
Al-Rifai, Sarah. „Rôle de la résistine hypothalamique dans l'installation de l’inflammation hypothalamique et l’insulino-résistance : impact de la consommation aigüe ou chronique d'un régime hyper lipidique“. Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS095/document.
Der volle Inhalt der QuelleObesity is closely linked to a cluster of metabolic disorders including chronic low-grade inflammation and insulin resistance, which constitutes a principal risk factor for type 2 diabetes. In rodents, cumulative evidence support that the consumption of high fat diet (HFD) is among the most important nutritional factors predisposing to obesity associated insulin resistance and low-grade inflammation. Indeed, HFD induces hypothalamic inflammation and deregulates energy homeostasis control through the alteration of hypothalamic insulin and leptin responsiveness, considered as the main anorexigenic hormones. In addition, it has been shown that unlike peripheral inflammation, which occurs as a consequence of obesity, hypothalamic inflammation develops selectively in the hypothalamic arcuate nucleus (ARC) within the first days of HFD exposure. These data suggest that hypothalamic inflammation is a critical step in the early onset of the deregulation of energy homeostasis by HFD. The cellular and molecular mechanisms underlying obesity-induced hypothalamic inflammation are still not fully characterized. In rodents, resistin is described as a causal factor in obesitymediated insulin resistance and type 2 diabetes. Resistin is mainly secreted by adipose tissue in rodents but an endogenous expression of resistin was also reported in the hypothalamus. However, its action at the central level is not fully understood. Our group recently demonstrated that central resistin, via hypothalamic TLR4, promotes overall insulin resistance through the promotion of inflammatory pathway. In this context, we aimed to investigate the role of resistin/TLR4 pathway in HFD-induced hypothalamic inflammation and insulin resistance. In the present study we report for the first time that both short and long term HFD are associated with a significant increase of resistin expression throughout the MBH. Our results revealed a transient increase in resistin mRNA expression in the ARC after 3 days of HFD, followed by a decline to baseline at day 8 and an expression that increases again after 8 weeks of HFD. We showed that the increase of resistin expression is concomitant with short term HFD-induced ARC reactive gliosis, known to early disrupt energy balance and to predispose to obesity. Interestingly, our results revealed that resistin is expressed by POMC neurons which are critical for energy balance and tanycytes that have the specificity to contact both cerebro-spinal fluid and fenestrated capillary in the mediane eminence. Interestingly, we show that resistin induces tanycytes inflammation through TLR4 suggesting that resistin could promote inflammation in tanycytes in response to short term HFD. Additionally, we show that ICV resistin markedly increases inflammatory markers in the hypothalamic arcuate nucleus in association with reactive gliosis involving recruitment of both microglia and astrocytes. Interestingly, we report that the knockdown of TLR4 almost completely abolished resistin-dependent both hypothalamic inflammation and reactive gliosis. Our data demonstrate that restitin/TLR4 pathway could play a critical role in HFD-diet induced hypothalamic inflammation in response to short and long term HFD which predispose to obesity, a hallmark of metabolic syndrome
Reininger, Laura. „Rôle des vésicules extracellulaires dans les altérations de l'homéostasie musculaire au cours du développement de l'insulino-résistance“. Electronic Thesis or Diss., Strasbourg, 2020. http://www.theses.fr/2020STRAJ064.
Der volle Inhalt der QuelleGlucose homeostasis is maintained through insulin-sensitive organs communication via hormones and cytokines. Extracellular vesicles appear to be a new player in the maintenance of glucose homeostasis. This communication is altered during insulin resistance that can lead to the development of type 2 diabetes. In the first part, we focused on the ELVs (exosomes like vesicles) of mice deficient for leptin (ob/ob mice) to determine the impact of skeletal muscle (SkM) insulin resistance (IR) associated with obesity on ELVs released, composition and biological impact on SkMs and adipocytes. In a second part, we study the impact of IR associated with inflammation (TNF-α) on exosomes and microparticles release, compositions and impact on SkMs and β cells. Our results demonstrate, in the context of IR associated with obesity, that ELVs have a modification of all their component and contribute to the propagation of signals inducing IR and cholesterol storage in SkM and adipogenesis in adipocytes. In the case of IR related with inflammation (TNF-α), our results demonstrate that microparticles and exosomes have specific biological functions which allow dissemination of TNF-α deleterious effects to SkMs and alter β cells insulin secretion. Taken together, this work contributes to the identification and a better understanding of new players involved in type 2 diabetes development, with the potential identification of new therapeutic targets
Alyanakian, Marie-Alexandra. „Rôles de l'immunorégulation et de l'environnement dans la physiopathologie du diabète auto-immun“. Paris 5, 2006. http://www.theses.fr/2006PA05D030.
Der volle Inhalt der QuelleThe major focus of our studies was the analysis the role of immunoregulation in the development of autoimmune diseases and more particularly of autoimmune insulindependent diabetes. To that aim we have used the experimental model of the NOD (non obese diabetic) mouse. We have developed our work around two essential themes. First, the detailed analysis of the phenotypic and functional characteristics of the main T cell subsets that control autoimmune responses. We have also attempted to study more in depth their antigen specificity using an adoptive transfer model. Secondly, we have described original models showing the protective effect on the development of autoimmune diabetes of certain components of infectious agents. The analysis of the immune mechanisms affording this protection revealed that regulatory T lymphocytes play a central role in the induction and/or the maintenance of the protective effect
Bertrand, Chantal. „Rôles de l'apeline et de l'EPA sur le métabolisme énergétique au cours de la résistance à l'insuline“. Toulouse 3, 2013. http://thesesups.ups-tlse.fr/3565/.
Der volle Inhalt der QuelleFaced with the increasing prevalence of type II diabetes, the development of new therapeutic strategies is one of the major public health issues. Our research group studies focus on apelin, an adipokine overexpressed in obesity, that is beneficial and improves insulin sensitivity in obese and insulin resistant mice, by acting essentially on the muscle lipid metabolism. However, the role of apelin on liver metabolism has not been addressed yet. We thus studied, in obese and insulin resistant mice, the effects of a chronic apelin treatment on the main hepatic metabolic functions, as well as the expression and the regulation of apelin receptor, named APJ, in different hepatic cell types. We have shown that glycogen stores were not modified, but hepatic steatosis was reduced by 40% after 4 weeks of apelin treatment. This was associated to a decreased gene expression of SREBP-1c and FAS, suggesting that de novo lipogenesis was reduced by this treatment. In addition, lipid oxidation and secretion of VLDL were decreased. These effects seem to be the consequence of the treatment on the global amelioration of insulin sensitivity, rather than a direct apelin effect on the liver. Indeed, even though APJ gene expression is increased in the liver of obese and insulin resistant mice, the immunofluorescence experiments did not reveal the presence of APJ in hepatocytes. However, the presence of APJ in another cell type doesn't rule out indirect effects on the hepatic metabolism. Eicosapentaenoic acid (EPA), a polyunsaturated fatty acid from the omega 3 family, is also able to improve insulin sensitivity and to reduce weight gain. Moreover, EPA is able to increase apelin expression in the adipose tissue. As apelin exerts beneficial metabolic effects in the muscle, we studied the regulation of the muscle apelin/APJ system by EPA, in mice fed with a high fat diet supplemented with EPA (3. 6% of total lipids). This diet, after 10 weeks, prevented the development of obesity, glucose intolerance, alterations in muscle metabolism, and increased apelin and APJ muscle expression. In vitro, EPA induced apelin expression but also its secretion, suggesting that apelin could be a myokine, and a potential mediator of EPA's beneficial effects in insulin resistance
Handgraaf, Sandra. „Prévention de l'obésité et du diabète de type 2 par les oestrogènes : rôle des fonctions transactivatrices du récepteur des oestrogènes alpha“. Toulouse 3, 2013. http://thesesups.ups-tlse.fr/2315/.
Der volle Inhalt der QuelleEstrogens play a crucial role in maintaining energy and glucose homeostasis by activating the nuclear estrogen receptor alpha ( ERa ). However it is essential to better understand the mechanisms of activation. The main objective of this thesis has been to study the roles of two transactivation functions (ERaAF-1 and ERaAF-2) that contribute to modulate the transcription of many genes in response to the activation of ERa. For this purpose, we have developed an experimental approach exclusively in vivo, based on the use of mouse models deficient in ERa (ERa-/-), in ERß (ERß-/-), or specifically invalidated for ERaAF-1 (ERaAF-10) or ERaAF-2 (ERaAF-20) functions, and subjected to an obesogenic diet. After confirming the crucial role of ERa, showing the abolition of the protective effect of oestradiol (E2 ) in ERa-/- mice and not ERa-/-, we showed that the beneficial effects of endogenous estrogen and administration of E2 on body composition, insulin sensitivity and glucose homeostasis are completely retained in the ERaAF-10model, but abolished in ERaAF-20mice. As previously demonstrated in terms of bone and vascular protection, the beneficial actions of estrogen on the body composition, insulin sensitivity and glucose tolerance appears independent function AF-1, but dependent AF -2 of ERa
Taverna, Mariano Javier. „Rétinopathie diabétique humaine : aspects génétiques et physiopathologiques“. Paris 6, 2005. http://www.theses.fr/2005PA066113.
Der volle Inhalt der QuelleNormand-Lauzière, François. „Anomalies postprandiales du métabolisme des acides gras libres dans l'évolution naturelle du diabète de type 2“. Mémoire, Université de Sherbrooke, 2010. http://hdl.handle.net/11143/5545.
Der volle Inhalt der QuelleSerre, Laurent. „Etude des mécanismes cellulaires et moléculaires responsables de la résistance à l'autoimmunité des souris NOD déficientes en TSSP“. Thesis, Toulouse 3, 2015. http://www.theses.fr/2015TOU30019/document.
Der volle Inhalt der QuelleIn the thymus, the presentation by thymic stromal cells (epithelial (TEC) or dendritic cells (DC)) of peptides derived from self-proteins associated with the major histocompatibility complex class II (MHC-II) is an essential mechanism for the development of CD4 T cells (CD4) and selection of their antigen receptor (TCR) repertoire. Thus, a low intensity interaction between the TCR expressed by thymocytes and pMHC complexes is necessary for the positive selection of thymocytes while a high affinity interaction lead to its deletion. The processing of proteins for MHC-II presentation pathway is dependent of sequential proteolysis involving a set of protease with a relatively imprecise specificity. Proteases can therefore promote or inhibit the generation of certain peptides that can bind to MHC-II molecules. The thymus specific serine protease (TSSP) is expressed in the thymus by cortical TEC and thymic DC, but not by DC in the periphery. Various studies suggest that TSSP is a protease of MHC-II presentation pathway which could limit, by some unknown mechanisms, the presentation of certain self-antigens in the thymus and in particular by DC. Thus, TSSP might limit self-tolerance in the thymus. In particular, we have shown that TSSP-deficient NOD mice (NOD Tssp°) are resistant to type 1 diabetes (T1D) correlated with an increased deletion of CD4 T cells specific for certain antigens associated with T1D. Thus, NOD Tssp° are partially tolerant to S100ß, a Langerhans islet antigen associated with the development of T1D. To better understand the impact of negative selection on the self-reactive repertoire, we analyzed the S100ß-specific CD4 T cells repertoire of NOD wildtype (WT) and NOD Tssp° mice. Although it's relatively diverse, the TCRaß repertoire presents, in both strains of mouse, a bias to low-avidity dominant and public TCRa rearrangements. High avidity CD4 T cells expressing a private repertoire are found in NOD WT mice but are selectively deleted in NOD Tssp° mice. Thus, increasing the availability of antigen promotes high avidity T cells deletion. In parallel, we analyzed the effect of the absence of TSSP on the development of another autoimmune disease mediated by CD4 T cells, the experimental autoimmune encephalomyelitis (EAE) induced by the MOG35-55 peptide. NOD Tssp° mice develop a less severe pathology than WT mice. This reduction of severity results, at least in part, in a decrease of avidity and functionality of encephalitogenic MOG35-55- specific CD4 T cells. Taken together, this work and previous studies from our team suggests that TSSP, by negatively regulating antigen presentation, prevents self-tolerance and thus promotes the emergence of a self-reactive TCR repertoire of high avidity for the antigen. In this context, maintaining TSSP during evolution is surprising. Nevertheless, the absence of TSSP also reduces the specific response against some non-self-antigens. Thus, in the thymus, TSSP by limiting self-tolerance would allow the diversification of the TCR repertoire
Taveau, Christopher. „Rôle de la vasopressine dans les troubles du métabolisme glucidique : possible impact dans le développement du diabète“. Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066211/document.
Der volle Inhalt der QuelleIt is well established that vasopressin (AVP) level is high in both human and experimental diabetes. In humans, several recent studies have shown an association between copeptin (biomarker of AVP secretion) and the occurrence of diabetes mellitus or hyperglycemia, metabolic syndrome and obesity. Our team has shown a reverse association between water consumption (decrease AVP secretion) and the risk of hyperglycemia in the general population (D.E.S.I.R cohort). The aim of my thesis was to determine the role of AVP and fluid intake in glucose homeostasis in healthy rats and in a rat model of metabolic syndrome. AVP, administered acutely or chronically in healthy rats, increases glycaemia and this effect is reversed by a V1a receptor antagonist. V1b receptor activation does not influence insulin secretion but stimulates moderately basal glucagon production by the pancreas. These effects were observed in two different healthy strains of rats. In obese Zucker rats, a high AVP level worsens fasting hyperinsulinaemia and glucose intolerance whereas hydration does not affect glucose tolerance but drastically reduces hepatic steatosis, the content of cholesterol and triglycerides in liver and expression of genes involved in hepatic lipogenesis. In conclusion, these studies show for the first time, that AVP aggravates glucose tolerance whereas a highly hydrated diet is protective. These results, in agreement with our epidemiological data, demonstrate a causal link between vasopressin and/or hydration and glucose metabolism disorders
Sotornik, Richard. „Régulation du flot sanguin dans le tissu adipeux sous-cutané“. Thèse, Université de Sherbrooke, 2018. http://hdl.handle.net/11143/11959.
Der volle Inhalt der QuelleAbstract : Subcutaneous adipose tissue (SCAT) is the preferential site of triacylglycerols (TAG) postprandial disposal. When the buffering capacity of SCAT for lipids is exceeded, TAG are disposed in ectopic adipose tissue depots and in non-adipose tissues, such as liver and muscles. Consequently, multiple dysfunctions of these organs and tissues develop including insulin resistance (IR). In obese people, the postprandial period is characterized by metabolic, immune and hormonal alterations, but also by severely altered adipose tissue blood flow (ATBF). Nevertheless, significant alteration of postprandial ATBF was also found in lean individuals with highly positive familiar history of cardiometabolic diseases (obesity, type 2 diabetes, cardiovascular diseases). In the thesis, we term them as "non-responders". Up to date, little attention has been payed to this phenomenon. The underlying hypothesis of this thesis is that alterations in ATBF are inborne or very early and that they participate on the development of IR, type 2 diabetes and metabolic syndrome. Consequently, the aim of our research was to verify if the alterations in ATBF are present in healthy, normal-weight subjects, but at very high risk for development of IR or cardiometabolic diseases. Simultaneously, we searched for factors linked with nonresponsiveness phenomenon. To do this, we examined some hormonal factors in ATBF regulation. Our results confirm the presence of altered fasting and postprandial ATBF in at highrisk subjects for cardiometabolic diseases, but still lean and metabolically healthy, without IR. For the first time, we have also demonstrated the role of cholinergic system in postprandial ATBF regulation, and vasodilatory effect of vasoactive intestinal peptide (VIP) in SCAT. However, none of these factors takes part in postprandial ATBF dysfunction in non-responders. Higher TAG levels repeatedly found in non-responders and the association of ATBF with some indices of insulin sensitivity described in the literature suggest that alteration of lipid metabolism as a result of low ATBF may mediate deterioration of insulin sensitivity.
Grenier-Larouche, Thomas. „Implication du stress du réticulum endoplasmique dans l'intolérance aux lipides observée dans le diabète de type 2“. Mémoire, Université de Sherbrooke, 2012. http://hdl.handle.net/11143/6310.
Der volle Inhalt der QuelleBarros, Monteiro Janice. „Déterminants génétiques de la résistance à l'insuline et du diabète sucré : exploration par SNP (single nucleotide polymorphism) de la calpai͏̈ne-10 et d'autres gènes candidats dans la population amazonienne du Brésil“. Montpellier 1, 2004. http://www.theses.fr/2004MON1T016.
Der volle Inhalt der QuelleMuñoz-Bellili, Naïma. „Identification de gènes associés à la prédisposition au diabète de type 2 et à l'insulino résistance : étude prospective D.E.S.I.R : exploration des systèmes rénine-angiotensine-aldostérone et kininogène kallicréine kinines dans la susceptibilité au diabète de type 2, hypertension et syndrome métabolique“. Paris 7, 2010. http://www.theses.fr/2010PA077035.
Der volle Inhalt der QuelleThe Renin-angiotensin-aldosterone System and kininogene kallicreine kinines play an important role in the renal fonction by autocrine or paracrine local action. The prospective studies on a large population are free of biases of cross-sectional studies or case-control. Our aims is to assess the impact of two polymorphisms - 344 T > C and 3097G > A of CYP11B2 gene, and to analyze the impact of two polymorphisms - 58 T > C and -2717 T > C of BDKRB2 gene, on prevalence and incidence of HT A, T2D and MS, in an issue of general population and tracks from 1994 to 2003 - D. E. S. I. R. Study. The genotyping was carried out by TaqMan. Our results show a significant association between the polymorphism 3097 G > A of CYP11B2 and the incidence of HT A, Risk for incident HT was reduced with the AA genotype of 3097 G>A, The prevalence of HT was lower in women carrying the C allele of-344 T>C. In men, incident T2D was associated with both polymorphisms, for the 3097 G>A: the AA genotype was associated with a lower risk. In men, incident MetS was associated with 3097 G>A, men AA was protect. Significant relationships between BDKRB2 -58 OT genotypes and prevalence and incidence of T2D were found. We noted t significant interaction between the -58 C> T and the ACE I>D in their association with T2D with subjects carrying the TT/DD genotype combination having the highest percentage of new-onset diabetes. The C-allele of the BDKRB2 -58 OT had a protective effect for T2D. In conclusion, variability of genes of the SRA is associated with the onset of the DT2, the HTA and metabolic syndrome, with a difference by gender. The variability of the SKK genes is associated with the DT2 in healthy people
Vella, Roxane. „Une exposition à l'ozone induit une insulino-résistance via un stress oxydant systémique et un stress du réticulum endoplasmique musculaire : pollution à l'ozone et diabète de type 2 : peut-on imaginer une origine environnementale aux maladies métaboliques ?“ Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10176.
Der volle Inhalt der QuelleA growing body of evidence suggests that exposure to traffic-related air pollution is a risk factor for type 2 diabetes. Ozone, a major photochemical pollutant in urban areas, is negatively associated with fasting glucose and insulin concentrations but most aspects of this association remain to be elucidated. Using an environmentally realistic concentration (0.8 ppm), we demonstrated that exposition of rats to ozone induced whole body insulin resistance and oxidative stress, with associated endoplasmic reticulum (ER) stress, JNK activation and disruption of insulin signaling in skeletal muscle. Bronchoalveolar lavage fluids from ozone-treated rats reproduced this effect in C2C12 myotubes, suggesting that toxic lung mediators were responsible for the phenotype. Pre-treatments with the chemical chaperone 4-phenyl butyric acid, the JNK inhibitor SP600125 or the antioxidant N-acetylcysteine alleviated insulin resistance, demonstrating that ozone sequentially triggered oxidative stress, ER stress and JNK activation to impair insulin signaling in muscle. This study is the first to report that ozone plays a causative role in the development of insulin resistance, suggesting that it could boost the development of diabetes. We therefore provide a potential mechanism linking pollutant exposure and the increased incidence of metabolic diseases
Berthou, Flavien. „La désensibilisation croisée des voies de signalisation de la leptine et de l'insuline au niveau central : lien possible entre leptino- (obésité) et insulino-résistance (diabète de type 2)“. Paris 11, 2009. http://www.theses.fr/2009PA11T108.
Der volle Inhalt der QuelleLacerte, Guillaume. „Impacts différentiels des changements de la distribution d'adiposité sur les variations de résistance à l'insuline et d'adiponectine chez des jeunes adultes avec un poids normal sur une période de 4 ans“. Mémoire, Université de Sherbrooke, 2014. http://hdl.handle.net/11143/6320.
Der volle Inhalt der QuelleMarcotorchino, Julie. „Effet protecteur de la vitamine D sur l'obésité et les désordres physiologiques associés“. Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4332.
Der volle Inhalt der QuelleWhite adipose tissue is not a simple energy reservoir, it also secretes several molecules called adipokines. In standard conditions, adipokines are involved in general homeostasis permitting the regulation of numerous functions and metabolic pathways. During the development of obesity, adipose tissue physiology is severely disrupted. This results in dysfunction such as low-grade inflammatory status. The accumulation of these disturbances within adipose tissue generates a dysregulation of adipokines secretion. This will have for consequences a failure of some metabolic pathways resulting in insulin-resistant state leading to type 2 diabetes. Several epidemiological studies show a link between vitamin D deficiency and numerous pathologies like cancers, immunity deseases or cardiovascular deseases. In addition, there is an inverse correlation between plasma levels of 25(OH)D and the prevalence of obesity, hypertension and type 2 diabetes. However, the link between vitamin D deficiency and obesity is not well established. The aim of this thesis is to better understand the link between vitamin D deficiency, obesity and physiological disorders associated. For this purpose, we have evaluated vitamin D effects on adipose tissue and adipocyte biology (inflammation, glucose uptake) and subsequently effects of vitamin D supplementation on diet-induced obesity. In a first study in vitro, we have showed an anti-inflammatory effect of vitamin D on adipocyte. This effect appears to be VDR-dependant and implies a modulation of NFκB signaling pathway. This study could partly explain le link between vitamine D deficiency and low-grade inflammation associated with obesity
Maimaitiming-Madani, Suliya. „Contribution du système des peptides natriurétiques à la prédisposition génétique au syndrome d'insulino-résistance et au diabète de type 2 dans la population française : études prospectives D.E.S.I.R. et DIABHYCAR“. Paris 7, 2010. http://www.theses.fr/2010PA077040.
Der volle Inhalt der QuelleThe natriuretic peptides System plays an important role in lipid metabolism and in blood pressure regulation. We evaluated the effect of polymorphisms at NPPA-NPPB locus in the metabolic syndrome, the intermediate phenotypes of this syndrome, the blood pressure, the risk of the hyperglycemia and the BNP plasma concentrations in a nine-year follow-up study in a general population in France, the cohort: DESIR. We also studied the associations of these polymorphisms with the blood pressure and the vascular complications of the type 2 diabetes in DIABHYC AR study. A replication study with 7 international populations was also carried out. Our results shown that the polymorphisms at NPPA-NPPB locus were associated with the metabolic syndrome, with several metabolic syndrome related traits, with the risk of hyperglycemia, with BNP plasma concentrations and the blood pressure in the DESIR study, and were associated with the blood pressure in DIABHYCAR study. There was no significant association with the vascular complications. In conclusion, the genetic variations at NPPA-NPPB locus were able to modify the BNP plasma levels and they were associated with the metabolic syndrome, the intermediate phenotypes of this syndrome, the hyperglycemia risk and the blood pressure. We suggest that even replicated and biologically plausible genetic association ?studies based or surrogate markers do not easily translate into clinically meaningful prognosis
Yepmo, Mélissa. „Signature unique de l’ARN circulaire dans les muscles squelettiques humains de différentes sensibilités à l’insuline“. Electronic Thesis or Diss., Strasbourg, 2023. http://www.theses.fr/2023STRAJ109.
Der volle Inhalt der QuelleCircular RNAs are a class of non-coding RNAs characterized by a covalently closed loop structure. Functionally, they can act on cell physiology by inhibiting microRNAs and regulating gene and protein expression. The emerging function of circRNAs is not fully understood, but initial studies have recently shown that they are involved in the regulation of insulin secretion. In this work we tried to identify circRNAs in skeletal muscle at the level of glycolytic and oxidative fibers in healthy and type 2 diabetic patients. Our results showed a unique circular RNA signature not only as a function of status (healthy or T2DM) but also as a function of muscle fibre type (triceps or soleus). For the first time, our study has been able to identify a new way of regulating gene and protein expression independently of what is already known in skeletal muscle. These results allowed us to identify new key molecules involved in the development of type 2 diabetes, with the potential to identify new therapeutic targets
Badin, Pierre-Marie. „Étude du rôle des lipases musculaires dans la régulation du métabolisme des lipides et de la sensibilité à l'insuline“. Toulouse 3, 2013. http://thesesups.ups-tlse.fr/2068/.
Der volle Inhalt der QuelleDuring my PhD thesis, we studied the pathophysiological link between skeletal muscle lipolysis and insulin-resistance. We also evaluated the role of skeletal muscle lipolysis in the regulation of lipid and oxidative metabolism. We have shown that the expression of adipose triglyceride lipase (ATGL) in skeletal muscle, a limiting enzyme of lipolysis, was negatively correlated with insulin sensitivity in a cohort of lean, obese and type 2 diabetic subjects. To study the effect of ATGL up-regulation on insulin sensitivity, we next over-expressed ATGL in human primary myocytes. Insulin-sensitivity and signaling were both reduced. We also showed that these effects were dependant on diacylglycerol (DAG) production and protein kinase C (PKC) activation. PKC are known to inhibit insulin receptor substrate 1 by serine phosphorylation. We next studied, in a murine mouse model, the effect of high fat feeding on insulin resistance and skeletal muscle lipase expression. We have shown an increase of comparative gene identification 58 (CGI-58) expression (a co-activator of ATGL) and a decrease of hormone sensitive lipase phosphorylation on its activating residue at serine 660. This deregulation of lipolysis was associated with a strong increase of total DAG concentration and PKC ? and e membrane translocationin skeletal muscle. In parallel to this work, we studied the metabolic role of CGI-58 in skeletal muscle through overexpression and knockdown studies in primary human myocytes. We have shown that CGI-58 is a co-activator of ATGL in skeletal muscle. Moreover we observed during the knockdown of CGI-58 a decrease of lipid oxidation and an increase of glucose oxidation. These effects were partly explained by the down-regulation of pyruvate dehydrogenase kinase 4 expression. These effects were mostly mediated by a decrease of peroxysome proliferator-activated receptor beta/d activation by fatty acid from lipolysis. Finally our work shows for the first time a pathophysiological link between lipases deregulation and insulin-resistance in skeletal muscle. These data also significantly contribute to a better understanding of the molecular and physiological regulation of skeletal muscle lipolysis
Ben, Amara Nisserine. „Evaluation du statut en micronutriments lipophiles au cours de l'obésité : relation avec l'inflammation et l'insulino-résistance“. Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM5053.
Der volle Inhalt der QuelleObesity is associated with chronic inflammatory condition that plays a deleterious role.This inflammatory state associated with obesity was involved in the development of metabolic complications : insulin resistance and T2DM.Obese, AT is a site for the production of pro and/or anti-inflammatory adipokines, and plays a major role in the development of chronic inflammation associated with obesity.Modifications and changes in lifestyle and therapeutic approaches are preferred to deal with obesity. However,preventive approaches should not be ignored,several epidemiological studies have shown a correlation between obesity and micronutrient deficiency.In addition,there is an inverse correlation between lipophilic micronutrients and carotenoids and the prevalence of obesity and T2DM.The purpose of this thesis is to understand the possible link between LM and carotenoids deficiency, obesity and associated physiological disorders.A cross-sectional study was performed in non-diabetic obese patients.The results allowed us to conclude the existence of a favorable effect of b-carotene on insulin sensitivity in obese patients.This effect may be related to modulation of inflammation or the expression of some adipokines(such as adiponectin), either directly or through its pro-vitamin A activity.A preclinical study was performed; the objective is to assess the impact of the vitamins on weight gain and insulin sensitivity.Mice were subjected to a hypovitaminic diet.After 10 weeks of regimen, we observed an increased adiposity and an altered insulin sensibility.This diet probably acts on the hepatic lipid metabolism via a decrease in oxidative capacity
Tubbs, Emily. „Importance of intracellular Mitochondria-Associated endoplasmic reticulum Membranes (MAM) in insulin-resistance“. Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10210.
Der volle Inhalt der QuelleMitochondria-associated endoplasmic reticulum membranes (MAM) are functional domains between both organelles involved in Ca2+ exchange, through the voltage-dependent anion channel (VDAC)-1/glucose regulated protein 75 (Grp75)/inositol 1,4,5-triphosphate receptor (TP3R)-1 complex, and regulating energy metabolism. Whereas mitochondrial dysfunction, ER stress, and altered Ca2+ homeostasis are associated with altered insulin signalling, the implication of MAM dysfunctions in insulin resistance is unknown. During my PhD, my work has underlined a new role of MAM in hepatic insulin- resistance. T have developed a quantitative method called in situ Proximity Ligation Assay to visualise and quantify the interactions between ER and mitochondria. T have shown that MAM integrity is required for insulin signalling and that disruption of MAM is implicated in hepatic insulin resistance. Preliminary data also suggest that MAM alterations are also associated with muscle insulin resistance. T have also identified the presence of the protein kinase B (PKB), a key protein involved in metabolic effects of insulin, at the MAM interface, and demonstrated that its phosphorylation by insulin is altered in this fraction in liver of diabetic mice. Lastly, T have also participated to the identification of: 1) the presence of cyclophilin D (CypD) at MAM interface which regulates calcium transfer from ER to mitochondria in both cardiomyocytes and hepatocytes, and 2) a regulation of MAM by glucose in liver, which is involved in the regulation of mitochondria dynamics and function during nutritional transitions. Consequently, my work improved the knowledge on the composition, function and regulation of MAM, and highlighted MAM as a potential new target for the modulation of hepatic insulin action and metabolism
Steiler, Tatiana L. „Cascades de signalisation dans la régulation de l'homéostasie du glucose“. Paris 6, 2005. http://www.theses.fr/2005PA066111.
Der volle Inhalt der QuelleArbin, Valérie. „Effets de l' inhibition mixte de l' enzyme de conversion de l' angiotensine I et de l' endopeptidase neutre 24-11 sur la résistance à l' insuline et le dysfonctionnement endothélial dans le diabète expérimental : rôle de la voie bradykinine - monoxyde d' azote“. Paris 5, 2002. http://www.theses.fr/2002PA05P604.
Der volle Inhalt der QuelleAngiotensin-converting enzyme (ACE) inhibitors may improve endothelial dysfunction in insulin-dependant diabetes mellitus [. . . ]
Chavez, Talavera Oscar Manuel. „Rôle des acides biliaires dans la physiopathologie de l'obésité, la résistance à l'insuline, le diabète de type 2, la stéatose hépatique non alcoolique et dans le contexte de la chirurgie bariatrique Bile Acid Control of Metabolism and Inflammation in Obesity, Type 2 Diabetes, Dyslipidemia, and Nonalcoholic Fatty Liver Disease Bile Acid Alterations in Nonalcoholic Fatty Liver Disease, Obesity, Insulin Resistance and Type 2 Diabetes: What Do the Human Studies Tell?” Bile acids associate with glucose metabolism, but do not predict conversion to diabetes Bile acid alterations are associated with insulin resistance, but not with NASH in obese subjects Roux-en-Y gastric bypass increases systemic but not portal bile acid concentrations by decreasing hepatic bile acid uptake in minipigs The functional relevance of bile acids in the improvement of HDL-mediated endothelial protection after bariatric surgery Metabolic effects of bile acid sequestration: impact on cardiovascular risk factors“. Thesis, Lille, 2019. http://www.theses.fr/2019LILUS057.
Der volle Inhalt der QuelleIn addition to their role in the solubilization of dietary lipids, bile acids are signaling molecules regulating their own metabolism, glucose and lipid homeostasis, energy expenditure, cardiovascular function and inflammation via the activation of the Farnesoid X Receptor (FXR) and the Takeda G protein coupled Receptor 5 (TGR5). Indeed, changes in bile acid concentrations are associated with metabolic diseases and therefore they are candidates to participate in the pathophysiology of these diseases or predict their progression.In the first part of this thesis, we studied bile acid changes in the context of obesity, insulin resistance, type 2 diabetes and non-alcoholic steatohepatitis. We demonstrated that bile acids are correlated with glucose homeostasis in humans, but that they are not predictors for the progression from prediabetes to type 2 diabetes in a longitudinal cohort study.In the second part of this thesis, we studied the bile acids in the context of bariatric surgery. Our results showed that bariatric surgery reduces the hepatic recapture of certain bile acids, causing them to increase in the systemic circulation. Additionally, we showed that it is not the bile limb but the common limb the one responsible for metabolic changes after bariatric surgery in the minipig. Finally, we showed in humans that bile acids linked to high-density lipoproteins (HDL) increase after bariatric surgery, and that this increase is correlated with the restoration of their vasoprotective functions
Harmel, Élodie. „Rôle et régulation de la protéine kinase AMPK au niveau intestinal“. Phd thesis, Université Claude Bernard - Lyon I, 2012. http://tel.archives-ouvertes.fr/tel-00934093.
Der volle Inhalt der QuelleLefevre, Camille. „Exploration fonctionnelle des cellules souches du tissu adipeux dans l'émergence des maladies de l'obésité“. Electronic Thesis or Diss., Lyon, 2020. https://n2t.net/ark:/47881/m6319v9s.
Der volle Inhalt der QuelleObesity induces a chronic inflammation responsible for complications (diabetes, cardiovascular diseases) where adipose tissue plays a central role. At the onset of obesity, inflammation is at low grade suggesting the control by immunosuppressive mechanisms that decrease with obesity, promoting complications. Adipose stem cells (ASC) support the development and the homeostasis of adipose tissue in subcutaneous and visceral adipose depots. Inflammatory stimuli induce immunosuppressive functions in ASC in vitro, but published data report that ASC isolated from inflammatory adipose tissues in established obesity have lost these properties. The role of ASC in the immune homeostasis of adipose tissue is poorly known. We made the hypothesis that immunosuppressive properties of ASC are induced since the onset of obesity and that their alterations contribute to complications. To address this question, I performed two protocols of diet induced obesity in mice and I explored the functions of ASC isolated from subcutaneous (S-ASC) and visceral (V-ASC) adipose depots. My results show major differences in the proliferation and the differentiation potential of ASC from distinct adipose depots, according to published data. We reveal that these differences correlate with distinct metabolomes, V-ASC having lower mitochondrial and higher glycolytic activity than S-ASC. Using this model, we studied the immunosuppressive functions of ASC in early obesity in both adipose depots. To this end we performed a kinetic of 6, 10 and 14 weeks of high fat diet (HF) in C57Bl/6 mice. This timing covered low grade inflammation progress from glucose intolerance with 6 weeks of diet in the absence of adipose tissue inflammation, to insulin resistance at 14 weeks of diet associated with visceral, but not subcutaneous, adipose tissue inflammation. My results show that at 6 weeks of HF diet, V-ASC attracted macrophages and inhibited the pro-inflammatory M1 polarization of these cells. At the same time, S-ASC completely suppressed the proliferation of activated T lymphocytes and strongly inhibited their migration. This study shows (i) that CSA from both adipose depots are activated by HF diet, independently of inflammation and diet time, (ii) that the induced immunosuppressive properties target distinct immune cells, (iii) that they are maintained with resistance to insulin. The analysis of adipose tissue composition showed that the ASC population decreased and had lower proliferation rate with HF diet. This indicate that at the onset of obesity, intrinsic properties of ASC were maintained in vitro but their environment altered their maintenance in both adipose depots. In a second protocol, I explored the consequences of maternal overnutrition during lactation on the properties of ASC in the adulthood. It has been reported that these conditions favorize the development of metabolic diseases in the offspring. We wondered whether ASC are targeted by maternal diet and develop long term alterations. I isolated S- and V-ASC from the offspring 6 weeks after weaning and I explored the influence of a HF post-weaning diet. RNA seq analysis showed that maternal diet altered the transcriptome of ASC in the adulthood and induced glucose intolerance, even in animal fed with a standard diet after weaning. Gene expression altered in ASC support cell death, metabolic stress, transcription, protein synthesis. Some genes are only affected by the mother’s diet. For genes associated with cell death, differential expressions induced by HF diet are increased when cumulated with mother’s HF diet. These results show that alterations of ASC precede the complications in the adult offspring. ASC can thus be programmed by maternal overnutrition and are the probable vectors of later adipose tissue dysfunctions
Barquissau, Valentin. „Fonctions mitochondriales et étiologie de la résistance à l'insuline dans le muscle : approches chez l'homme et sur modèles animaux“. Clermont-Ferrand 1, 2010. http://theses.clermont-universite.fr/nondiff/2010CLF1MM14.pdf.
Der volle Inhalt der QuelleMitochondrial functions in the aetiology of muscle insulin resistance : clinical and animal studies. Altered mitochondrial oxidative capacities may be involved in the aetiology of muscle insulin resistance, thus promoting onset and development of type 2 diabetes. This work aimed at determining how obesity, high fat diet and oxidative stress respectively influence skeletal muscle insulin sensitivity and mitochondrial function. In a human study, we found that mild obesity is characterized by normal insulin sensitivity and a raise in mitochondrial respiration, whereas severe obesity is linked to insulin resistance and decreased mitochondrial respiration and ATP production. In Wistar rats fed a high fat diet for 14 days, insulin sensitivity was not altered while mitochondrial function was stimulated. Extending high fat diet to 40 days is accompanied by a decline in insulin sensitivity concomitantly with decreased mitochondrial respiration. In twelve-month-old SAM mice, exhibiting spontaneous chronic oxidative stress, mitochondrial respiration and muscle insulin sensitivity are stimulated compared to control mice. In the three models described, mitochondrial function modifications occur without any change in muscle mitochondrial content. In conclusion, this work evidenced that mitochondrial function adapts intrinsically to environmental conditions associated with the pathogenesis of type 2 diabetes. Following energy excess, mitochondrial function is first stimulated which may allow protecting from insulin resistance, potentially through a mild and beneficial oxidative stress. Thereafter, when obesity increases or high fat diet is extended, other regulatory pathways take place and lead to simultaneous alterations in insulin sensitivity and mitochondrial function
Pierron, Anne. „Étude des effets des produits de glycation dans le développement de la résistance à l'insuline“. Nice, 2006. http://www.theses.fr/2006NICE4049.
Der volle Inhalt der QuelleIn diabetic patients, chronic hyperglycemia leads to an increase in the formation of glycation products, which are termed AGEs (advanced glycation end-products). These modifications alter the function of these molecules and lead to deleterious cellular effects. AGEs are implicated in the development of insulin resistance and in diabetic complications, particularly diabetic retinopathy. In the work presented in my thesis, we have studied and compared the effect of two glycation products, human glycated albumin (HGA) and methylglyoxal (MGO), on insulin signaling pathways in retinal cells (ARPE-19) and muscular cells (L6). HGA is an early glycation product that exerts its effects via its fixation on an extracellular receptor, initiating intracellular signals. MGO is a highly reactive degradation product of glucose, and a major precursor of intracellular AGEs. Our results show that these two glycation products rapidly and differentially alter insulin signaling pathways. In presence of HGA or MGO, insulin-induced stimulation of the MAPK pathway is unchanged, whereas the insulin-induced PI3K/PKB pathway is inhibited. Fixation of HGA on RAGE receptor induces the formation of a RAGE - IRS-1 - PKCa complex. Formation of this complex induces the activation of PKCa and the phosphorylation of IRS-1 on specific serine residues, inhibiting the metabolic pathway of insulin. The intracellular increase of MGO induces the formation of IRS-1 adducts, leading to the inhibition of the metabolic pathway, probably due to structural modifications of IRS-1. Our results suggest that glycation products play a crucial role in the development of insulin resistance and in diabetic complications
Emanuelli, Brice. „Identification de socs-3 comme un nouvel élément de la voie de signalisation de l'insuline : implication dans les mécanismes de résistance à cette hormone“. Nice, 2002. http://www.theses.fr/2002NICE5756.
Der volle Inhalt der QuelleObesity is associated with insulin resistance, which may result in type 2 diabetes. We have identified the SOCS-3 protein as a new element of the insulin signaling pathway. The recently discovered SOCS proteins were originally described as cytokine signaling inhibitors. We have shown that SOCS-3 is a new insulin-target gene, and that its transcription occurs in a STAT5b-dependent manner. In return, SOCS-3 interacts with the insulin receptor and inhibits the insulin-induced DNA binding activity of STAT5b and tyrosine phosphorylation of IRS-1. These results indicate that SOCS-3 inhibits insulin signaling. Interestingly, we observed an increase in SOCS-3 expression in adipose tissue of obese and insulin resistant mice and demonstrated that SOCS-3 expression in obesity is dependent upon TNF-alpha, which plays a well-established role in obesity-related insulin resistance. Taken together, our results suggest that SOCS-3 is a new mediator of insulin resistance, that develops during obesity
Renaudin, Corinne. „Effets de l'insuline et du glucose sur l'hémodynamique microcirculatoire : étude chez des rats sains, diabétiques ou insulino-résistants“. Lyon, INSA, 1998. http://www.theses.fr/1998ISAL0052.
Der volle Inhalt der QuelleThe aim of this study was to determine if hyperglycemia associated with hyper-insulinemia, as there are observed in postprandial situations, may exert, in addition to their metabolic effects, microvascular hemodynamic effects on normal, diabetic (STZ) or insulin resistant rats (fructose 10% in drinking water). In fasted anesthetized rats, the spihotrapezius muscle was isolated and exteriorized for in situ visualization of the skeletal precapillary arterioles (diameter < 20 μm) by intra-vital microscopy in transillumination. The diameter and the vasomotion were recorded and measured (using offline a image processing analysis) during basal period and after intravenous infusion of glucose (1. 5 g/kg) or isotonic saline. Glucose infusion induced an elevation of hyperglycemia and hyper-insulinemia associated to a vasoconstriction and to an elevation of arterioles presenting vasomotion in normal rats whereas no vasoconstriction was observed in STZ rats and Fructose rats. Moreover, the vasomotion was not stimulated by glucose in these animals which also showed a glucose uptake defect. Our results suggested that in prediabetic or diabetic states, the lack of arteriolar vasoconstriction and vasomotion which occurs during hyperglycemie episodes could contribute to capillary hyperperfusion which, repeated, may favor the evolution of microvascular complications and, in addition, may contribute to glucose intolerance of muscular tissues
Macari, Françoise. „Déterminisme génétique de la résistance à l'insuline : identification de défauts moléculaires dans les syndromes de type A, d'Alström et des ovaires polykystiques“. Montpellier 1, 1999. http://www.theses.fr/1999MON13505.
Der volle Inhalt der QuelleGrigorescu, Florin. „Rôle des altérations de la structure et de la fonction protéine-kinase du récepteur à l'insuline dans la pathogénie de la résistance à l'insuline“. Montpellier 2, 1989. http://www.theses.fr/1989MON20132.
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