Dissertations / Theses on the topic 'Diabète de type 1 – chirurgie'
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Maanaoui, Mehdi. "La greffe d'îlots pancréatiques chez le patient diabétique transplanté rénal." Electronic Thesis or Diss., Université de Lille (2022-....), 2023. https://pepite-depot.univ-lille.fr/ToutIDP/EDBSL/2023/2023ULILS071.pdf.
Pancreatic islet transplantation is an innovative cellular therapy for the management of diabetes in patients with type 1 diabetes. Currently, there are few studies that address the prognostic impact of islet transplantation in patients with type 1 diabetes who have received a kidney transplant or the determinants of transplantation success in this population. Furthermore, the definition of diabetes is evolving, with the dichotomy between type 1 and type 2 diabetes fading in favor of diabetes classifications based on the patient's clinical and biological phenotype. Pancreatic islet transplantation could potentially be expanded to other profiles of patients with diabetes and a kidney transplant, especially if there's evidence of insulin secretion deficiency. Thus, the objective of this thesis is to determine the role of pancreatic islet transplantation in patients with diabetes and a kidney transplant.In the first section, we present the results of a nationwide cohort study assessing the effect of pancreatic islet transplantation following kidney transplantation compared to insulin alone in patients with type 1 diabetes. Islet-after-kidney recipients were matched to control patients using a time-dependent propensity score. After matching, pancreatic islet transplantation is associated with a reduction in the combined risk of death and return to dialysis, as well as the isolated risk of death. This study emphasizes the importance of considering islet transplantation as a full-fledged therapeutic alternative, especially in regions where it is not reimbursed or available.The second section explores the determinants of islet loss of functionality, in particular the repercussions of alloimmunity. The results of a single-center study suggest that preformed DSA and early de novo DSA have little impact on islet transplantation outcomes, but late de novo DSA is temporally associated with impaired metabolic results. No cases of cross-sensitization between pancreatic islets and the underlying kidney in recipients were described, neither in the study nor in the literature.The last section focuses on evaluating the insulin profile in patients with type 2 diabetes and a kidney transplant, through the calculation of HOMA-2 scores, to extract the impact of insulin secretion. Analysis of a single-center retrospective cohort shows an association between insulin resistance evaluated by HOMA-2 and the risk of allograft loss, while insulin secretion was only associated with metabolic balance. However, given the relationship between metabolic balance and the likelihood of death and graft loss in kidney transplant patients with diabetes, pancreatic islet transplantation could be part of the therapeutic arsenal in a personalized medicine approach for these patients.In conclusion, this thesis advocates for personalized diabetes medicine in kidney transplant patients, promoting the integration of pancreatic islet transplantation as a key component in the therapeutic strategy for these individuals
Chopard-Lallier, Sophie. "Suivi fonctionnel de la greffe d'îlots de Langerhans : interêt de l'imagerie IRM et de l'immuno-monitoring cellulaire." Thesis, Besançon, 2013. http://www.theses.fr/2013BESA3001.
Langerhans islet transplantation allows curingtype 1 diabetes by restoring an endogenous insulin secretion. Halfof patients will resume insulin withinyears. This loss of function may be explained by the lack of monitoring tools able to diagnose an ongoing graft failure. The aims of our work were toevaluate the efficiency of MRI to diagnose islet graft rejection, and to assess the feasibility of immune cellular monitoring in transplanted patients.MRI in the rat mortelMethods: Syngeneic, allogeneic and xenogeneic islets were transplanted intra-portally to diabetic rats after labeling with superparamagnetic ironoxide nanoparticles (ferucarbotran). Images were acquired on a clinical 3T MRI scanner.Results: The signal decreasing was different between the 3 types of transplantations. At day 4, the MRI signal in allogeneic group was significantlylower while glycaemia remained normal. With a cut-off value of 84% at day 4, sensitivity of 91% and specificity of 70% were obtained.Cellular immune monitoringMethods: Mixed lymphocyte cultures were performed with peripheral blood mononuclear cells from recipients and splenocytes from donors. Immunereactivity was assessed by the release of IFNy (ELISpot), cell prolifération (flow cytometry of Ki67), and cytokine quantification (Bioplex). Theresults were correlated to the islet graft function assessed by (5-score.Results: Patients with low islet function showed higher cellular reactivity against donor cells assessed by ELISpot IFNy ((p=0,007, r=-0,50) andproliferation index (p=0,006, r=-0,51). Patients with low graft function had higher levels of IFNy, IL-5 and 1L-17
Sterkers, Adrien. "Evaluation pré-clinique et clinique de l'autogreffe intramusculaire d'îlots de Langerhans." Phd thesis, Université du Droit et de la Santé - Lille II, 2013. http://tel.archives-ouvertes.fr/tel-00951952.
Plourde, Charles-Étienne. "Les mécanismes de résolutions du diabète de type 2 induits par la chirurgie bariatrique." Mémoire, Université de Sherbrooke, 2015. http://hdl.handle.net/11143/6038.
Duchatelet, Sabine. "Recherche de gènes de prédiposition au diabète de type 1." Paris 6, 2006. http://www.theses.fr/2006PA066254.
Type 1 diabetes (T1D) is an autoimmune multifactorial disease. We used 3 strategies to find T1D susceptibility genes : the study of IDDM4 locus previously mapped on chromosome 11q13 by linkage, the search for genes responsible for monogenic syndromes with diabetes, and candidate gene approach. The study of IDDM4 locus led to identify variants associated with T1D, and to precisely bound the critical region. Our genetic studies, supplemented by functional studies, will allow us to detect the susceptibility gene at IDDM4 locus. Besides, we identified PTHR1 and GLIS3 genes responsible respectively for Eiken and NDH syndromes. We tested PTHR1 as a candidate gene, and a functional polymorphism in FCRL3 gene, reported as associated with several other autoimmune diseases, in the susceptibility to T1D. We did not detect significant association. Identification of T1D susceptibility genes will provide a better understanding of pathological processes involved in the development of the disease
Magdelaine, Nicolas. "Diabète de type 1 du modèle ... à la boucle fermée." Thesis, Ecole centrale de Nantes, 2017. http://www.theses.fr/2017ECDN0034.
For people living with type 1 diabetes, today’s treatment consists of a number of daily insulin injections in order to have a limited glycemic excursion. Poorly controlled glycemia leads to long term complications. In patient’s everyday life, functional insulin therapy helps patients to adjust insulin doses. The artificial pancreas could significantly improve glycemia equilibrium by means of an automated insulin infusion using continuous glucose monitoring. The first contribution of this thesis is a new model of the metabolism for type 1 diabetic. The interpretation of this model allows to compute the tools for the functional insulin therapy. Thus it becomes possible to advise the patient on how much insulin to inject. The ongoing clinical study will evaluate the impact of the model. The second contribution is a control-law that guaranties both hypoglycemia avoidance and positivity of the injection for the first time. It is inspired from the clinical practice. The theoretical proof makes use of the theory of positively invariant sets. The Hypo-Free Hyper-Minimizer is designed to regulate glycemia in a hybrid closed-loop whereas the Dynamic Bolus Calculator is designed for the fully-automated artificial pancreas. This control-law gathers clinical practice, artificial pancreas hard constraints, and theoretical proof and is being protected through a patent
Senée, Valérie. "Recherche de gènes de prédisposition au diabète de type 1." Paris 7, 2002. http://www.theses.fr/2002PA077174.
Dubois-Laforgue, Danièle. "Déterminisme génétique de l'expression phénotypique du diabète de type 1." Paris 5, 2002. http://www.theses.fr/2002PA05N112.
The genetics of type 1 diabetes (DT1) remains elusive. About twenty susceptibility regions have been localized by genome scans, of wich a minority have been confirmed. Moreover, causal genes remain to be characterized. Association studies have been more contributive, since they demonstrated the implication of HLA genes and of the insulin VNTR and suggested that of CTLA4 and IL-12B. One of the difficulties in studying genetics of DT1 relies in the phenotypic heterogeneity of the disease. We studied the genetics of type 1 diabetes and of its phenotypic expression through the study of three genes, SDF-1, PARP and NOTC, which constitue putative candidates because of their function and their localization in regions. .
Diaz, Valencia Paula Andrea. "Épidémiologie du diabète de type 1 : incidence mondiale et ses déterminants." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066698/document.
Background: The increase of worldwide incidence of type 1 diabetes (T1D) was calculated to be on average 3.0% per year and it was predicted that it would be 40% higher in 2010 in children aged 0-14 years. The causes of this increase are still under study; this thesis updates our current knowledge on the global incidence of T1D, and taking advantage of the increasing availability of public databases examines the correlation between incidence and country characteristics. Methods: A comprehensive systematic literature search of published articles on the incidence of T1D worldwide was conducted to study global variations of the incidence within countries. The initial goal of this thesis was to study the correlation between environmental variables available in public databases with the country incidence of T1D. Conclusions and implications: During this thesis, we quantified the country-to-country variation in T1D incidence worldwide in children and adults, and show that a large part of this incidence could be accounted for by the variability of environmental factors within the countries taking advantage of the increasing availability of public databases. Environmental factors may be involved in the strong cohort effect we found; it is advisable to deepen the research on pregnancy and neonatal period and its implications on T1D. Here we could quantify that the increase of T1D was even larger than had been predicted in an earlier study
Sauter, Pierre. "Infection à coxsackievirus B4 dépendante d'anticorps et diabète de type 1." Lille 2, 2008. http://www.theses.fr/2007LIL2S038.
Nel, Isabelle. "Les cellules MAIT dans le diabète de type 1 chez l'homme." Electronic Thesis or Diss., Université Paris Cité, 2019. http://www.theses.fr/2019UNIP5156.
T1D is an autoimmune disease that involved both innate and adaptative immune system and in which intestinal homeostasis is altered. MAIT cells are innate-like T lymphocytes that recognize MR1-presenting ligands from bacterial origin, strongly interacting with gut microbiota. T1D is one of the most common chronic disease of the childhood, however T1D concerns both adults and children. To determine MAIT cells involvement in T1D physiopathology, circulating MAIT cell frequency, phenotype and function were analyzed by flow cytometry separately in children and in adult T1D. Frequency of MAIT cells from children at the onset of T1D is decreased and might reflect their migration from blood to inflamed tissues or their sustained activation leading to cell exhaustion. Interestingly, in adult T1D MAIT cell alterations are more pronounced in adults with established T1D as in adults at the onset of the disease. These data are in agreement with the emerging idea of disease heterogenity between T1D patients according to their age, probably involving different physiopathological mechanisms. Altogether, these data in humans support a potential involvment of MAIT cells in T1D physiopathology as already shown in NOD mice. Moreover, MAIT cell alterations have been detected in patients before the onset of T1D indicating MAIT cells might represent a new biomarker for the development of T1D. Finally, we hypothesize MAIT cells could also be involved in the insidious steps leading to develoment of diabetes complications, since MAIT cell alterations are more pronounced in adults as in children with established T1D. Further studies are needed however it clearly appears MAIT cells could become a new therapeutic way in next decades
Dubé, Marie-Christine. "Diabète de type 1 et contrôle glycémique : au-delà de l'hémoglobine glyquée." Thesis, Université Laval, 2006. http://www.theses.ulaval.ca/2006/23794/23794.pdf.
Novak, Jan. "Rôle des lymphocytes TNK dans le développement du diabète de type 1." Paris 5, 2005. http://www.theses.fr/2005PA05D008.
NKT cells, unconventional T cells restricted by theCD1d, molecule,have regulatory functions. Teir failures were implicated in the pathogenesis of several autoimmune diseases including TIDM. The experimental strategies based on the reconstitution or stimulation ofNKT cells have beneficial effect on the disease course. We investigated the mechanism of the protection from T1DM by NKT cells. Our data reveal that NKT cells block the differentiation of naïve anti-islet Tcells into effectors and their capacity to kill pancreatic β cells. The inhibitory action of NKT cells is independent of cytokines produced by NKT cells. Instead, cell contacts are required for the inhibition by NKT cell. The inhibition by NKT cells does not require their interaction with CD1d, contrarily to the involvement of this interaction in NKT cell development and several other functions
Dao, Thi Mai Anh. "Inflammation intestinale et diabète de type 2 : effet du Resveratrol." Thesis, Aix-Marseille 2, 2011. http://www.theses.fr/2011AIX22956.
The TD2 is characterized by a low-grade inflammatory state that impairs the secretion and action of insulin. Environmental pollutants such as POP (Persistent Organic Pollutants) and the change in gut flora induced by a high fat diet (HFD), are suspected to play an important role in the installation of this inflammation.The intestine is one of the first tissues exposed to pathogenic bacteria and some POP. This organ is also the first take part in the regulation of glucose homeostasis. So, it is reasonable to assume that chronic inflammation of the bowel may affect the development of TD2. Our objectives were: to assess the role of inflammation in the enterocyte development of diabetes TD2 and clarify the effect of Resveratrol (RSV) on the disease.Our results suggest that intestinal inflammation is involved in the establishment of a TD2. This inflammation could affect TD2 through releasing inflammatory cytokines, reducing the concentration of GLP-1 and promoting the passage of diabetogenic factors from the intestine to target tissues of insulin. The induction or reduction of intestinal inflammation by factor inflammatory (BaP) or anti-inflammatory (RSV) are respectively associated with worsening or improvement of the diabetic state.We also showed that the RSV could improve the diabetic state by normalizing the intestinal flora modified by diet and HFD, by increasing the concentration of GLP-1. In addition, co-administration of sitagliptin with RSV, an inhibitor of the enzyme DPP4,which degrade GLP-1, shows a potentiation of the effect of RSV in the sitagliptin: These results open the door for the use of RSV in the prevention and treatment of TD2.Keywords: Resveratrol, type 2 diabetes
Brezar, Vedran. "Beyond the hormone : antoimmune targeting of insulin other betacell antigens in type 1 diabetes." Paris 5, 2011. http://www.theses.fr/2011PA05T043.
Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease leading to destruction of insulin-producing β-cells. Insulin is a major target of islet-reactive T cells. Despite encouraging results obtained in non-obese diabetic (NOD) mice, clinical trials using subcutaneous insulin for preventing T1D have been largely unsuccessful. We show that this unsuccessful translation from mouse to human may be due to the low insulin dose used in clinical trials. Moreover, no long-term benefit was observed even at high insulin doses, suggesting that this may not be the optimal strategy for future T1D prevention trials. Besides insulin, other β-cell antigens (Ags) are involved in T1D autoimmunity. One of these Ags, islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)206-214 is highly immunodominant in NOD mice and is able to induce robust CD8+ T-cell responses even when contaminating other peptides in trace amounts. Beta-cell antigen identification may also lead to new hypotheses on T1D pathogenesis, most importantly on the elusive environmental factors triggering disease. We observed a high prevalence of antibodies against Mycobacterium avium paratuberculosis (MAP) among Sardinian T1D patients and identified two key epitopes cross-reactive with the β-cell Ag zinc transporter 8 (ZnT8). These results suggest that a molecular mimicry mechanism may precipitate T1D in MAP-infected individuals
Simoni, Yannick. "L’immunité innée dans le diabète sucré." Thesis, Paris 5, 2013. http://www.theses.fr/2013PA05T074/document.
The 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
Atlan, Catherine. "Le diabète de type 1 autoimmun : du laboratoire à la clinique : études chez la souris NOD des mécanismes cellulaires précoces." Aix-Marseille 2, 1999. http://theses.univ-amu.fr.lama.univ-amu.fr/1999AIX20674.pdf.
Jlali, Islem. "Le diabète de type 1 et le diabète de type 2, deux acteurs de déconditionnent physique : implication de la fonction pulmonaire et de l'oxygénation musculaire et cérébrale." Electronic Thesis or Diss., Université de Lille (2022-....), 2023. https://pepite-depot.univ-lille.fr/ToutIDP/EDBSL/2023/2023ULILS076.pdf.
Diabetes is a complex metabolic condition characterized by disruption of glucose and lipid metabolism. This metabolic alteration has structural and functional repercussions on several target organs such as the lungs and muscle and cerebral tissue. The literature about impaired pulmonary function as well as muscle and cerebral dysfunction in individuals with diabetes, is very large and sometimes contradictory. Furthermore, these alterations can manifest in daily situations, such as exercise, and are frequently associated with micro- and macrovascular complications of diabetes. Although regular exercise is known to improve glycemic control and consequently limit micro- and macroangiopathy, often individuals with diabetes have limited aerobic fitness and exercise intolerance.The main objective of this thesis work was to evaluate the impact of diabetes and chronic hyperglycemia on several stages of the oxygen transport chain at rest and during exercise in individuals with diabetes free from micro and macrovascular complications.In a first part, we examined the effect of diabetes on pulmonary function at rest, by measuring pulmonary flow and volumes using spirometry, as well as alveolar capillary diffusion capacity. Our results showed that, at rest, people with type 1 diabetes (T1D) had values comparable to those of healthy subjects for alveolar capillary diffusion capacity. Furthermore, in individuals with type 2 diabetes (T2D), lung flow and volumes were similar to those of healthy individuals and were not altered, even after maximal exercise.In a second part, we looked at ventilatory responses and muscle and cerebral oxygenation during maximal incremental exercise. We observed, in individuals with T1D, that tidal volume was reduced during maximal exercise, which could explain the altered maximum oxygen consumption (VO2max). This altered VO2max is also observed in people with T2D who present a reduced deoxyhemolobin (HHb) and a reduced total hemoglobin (Hbtot) reflecting impaired blood volume in the active muscle. Furthermore, in people with T2D, we observedalterations in cerebral hemodynamics, characterized by a decrease in oxyhemoglobin (HbO2) and total hemoglobin during maximal exercise.In conclusion, our results highlight that, although alterations in pulmonary function are still absent at rest, subclinical alterations appear in muscle and cerebral oxygenation during exercise in individuals with diabetes, even in the absence of micro and macrovascular complications. The research work of this thesis contributes to a better understanding of the mechanisms underlying the functional limitations observed in individuals with diabetes and opens perspectives for more targeted management of their metabolic and cardiorespiratory health
Reynier, Frédéric. "Génomique du diabète de type 1 : contributions à l'étude de l'étiopathogénie et des complications." Lyon 1, 2007. http://www.theses.fr/2007LYO10074.
Fourcade, Gwladys. "La greffe d'ébauches pancréatiques fœtales comme alternative thérapeutique dans le diabète de type 1." Paris 6, 2012. http://www.theses.fr/2012PA066392.
Transplantation of adult pancreatic islets has been proposed to cure type 1 diabetes. However, it is rarely considered in the clinic because of its transient effect on disease, the paucity of donors, and the requirement for strong immunosuppressive treatment to prevent allogeneic graft rejection. Transplantation of fetal pancreases may constitute an attractive alternative because of potential abundant donor sources, possible long-term effects due to the presence of stem cells maintaining tissue integrity, and their supposed low immunogenicity. In this work, we studied the capacity of early fetal pancreases from mouse embryos to develop into functional pancreatic islets producing insulin after transplantation in normoglycemic recipients in syngeneic and allogeneic conditions. We found that as few as 2 fetal pancreases were sufficient to control type 1 diabetes in a syngeneic context. Surprisingly, their development into insulin-producing cells was significantly delayed in male compared to female recipients, which may be explained by lower levels of prolactin in males. Finally, allogeneic fetal pancreases were rapidly rejected, even in the context of minor histocompatibility disparities, with massive graft infiltration with T and myeloid cells. This work suggests that fetal pancreas transplantation remains an attractive therapeutic option of type 1 diabetes but would require immunosuppressive treatment
Sanchez, Manuel. "Oxydation de l’ADN, longueur des télomères, et complications vasculaires du diabète de type 1." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS368.
Introduction: The purpose of this study is to assess the association between (i) 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidation; (ii) leukocyte telomere length (LTL); and (iii) allelic variations of genes involved in DNA oxidation and LTL; with the occurrence of renal and vascular complications in people with type 1 diabetes. Participants and Methods: The GENEDIAB and GENESIS cohorts included 494 and 662 participants with an average follow-up of 9.3 and 6.3 years, respectively. Plasma concentrations of 8-OHdG were measured at baseline and 27 SNPs were genotyped in both cohorts. LTL was measured by Q-PCR at baseline in the GENEDIAB cohort. Results: Higher concentrations of 8-OHdG were associated with lower GFR, higher albuminuria at baseline, and a higher risk of end-stage renal disease (ESRD) during follow-up. Minor alleles A of rs7675998 (NAF1), rs2125173 and rs10506083 (BICD1) were associated with a high risk of ESRD during follow-up. LTL was not associated with the risk of ESRD. In contrast, participants with the shortest telomeres and the highest concentrations of 8-OHdG had a higher risk of lower limb amputation. Conclusion: High concentrations of 8-OHdG and NAF1 and BICD1 polymorphisms are associated with the severity of diabetic nephropathy in 2 cohorts of type 1 diabetic patients. LTL appears to be an independent marker of amputation risk, as well as 8-OHdG
Pérol, Louis. "Immunothérapie par faibles doses d'IL-2 : potentiel therapeutique dans le diabète de type 1." Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066328.
CD4+ Foxp3+ regulatory T cells (Treg cells) are essential for the maintenance of immune tolerance. Interleukin-2 (IL-2) is mandatory for the homeostasis of Treg cells and its administration at low-doses induces a specific dose-dependent boost of Treg cells. Previous work has demonstrated that a short-tem treatment with low-doses IL-2 can revert established autoimmune diabetes in the NOD mouse model. However, this strategy induces long-term reversal in only 30% of the treated mice and can be optimized. During my PHD, my work has focused on the optimization of T1D therapy with low-doses of IL-2. First, we tried to combine low-doses of IL-2 with rapamycin, an immunosuppressive drug known to mainly affect Teff cells. The combined treatment (IL-2/Rapa) did not induce diabetes reversal and even reversibly broke IL-2-induced tolerance. Then, we tried to increase the IL-2 dose in order to increase the amplitude of the Treg boost. However, despite an important Treg cell boost, high-doses IL-2 administration to pre-diabetic NOD mice was toxic and precipitated T1D onset. In a second project, we described the existence of neutralizing anti-IL-2 autoantibodies in NOD mice and T1D patients. Our data suggested that anti-IL-2 autoantibodies negatively impacted on Treg cell homeostasis in vivo, contributing to the impaired immune tolerance observed in NOD mice and T1D patients. Altogether, our results lead to the consideration of low-doses IL-2, alone or combined, for the treatment of T1D. In addition, our demonstration of the existence of anti-IL-2 autoantibodies in NOD mice and T1D patients leads to a better understanding of T1D physiopathology
Lebailly, Basile. "Implication du gène Arntl2 lié au rythme circadien dans le diabète de type 1." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066340/document.
The Arntl2 gene (Aryl hydrocarbon Receptor Nuclear Translocator-Like 2) on which our lab focus is a transcription factor linked to the circadian rhythm which has been identified as a candidate gene to type 1 diabetes. Amongst the genes regulated by this transcription factor there is a strong candidate gene: the Interleukin 21, responsible of the proliferation of the T CD4+ lymphocyte, contributing to the destruction of the β cells in the pancreas during type 1 diabetes. My thesis project consisted on studying how the NOD and C3H alleles of Arntl2 control the expression of Il-21 and how it affected the immune system. The analysis of the immune cells revealed that the mice with a C3H allele in Idd6.3 produce less CD4+, CD8+ and CD4+IL-21+ T cells than the mice with a NOD allele in Idd6.3 and the NOD.B6 Arntl2-/-. We showed that this difference is due to the fact that ARNTL2 binds specifically to the RNA POL II binding site on the Il-21 promoter and inhibits its expression. We also have shown that a Knockout of this gene increase the apoptosis resistance of the thymocytes. And that this resistance was due to IL-21, indeed, injections of IL-21 brought the same increase in resistance than the one in the strains without a functional version of Arntl2. These new results show an unexpected role for Arntl2 in the regulation of the immune equilibrium by its control of Il-21 expression, and in the thymic selection of T cell by apoptosis
Lebailly, Basile. "Implication du gène Arntl2 lié au rythme circadien dans le diabète de type 1." Electronic Thesis or Diss., Paris 6, 2015. http://www.theses.fr/2015PA066340.
The Arntl2 gene (Aryl hydrocarbon Receptor Nuclear Translocator-Like 2) on which our lab focus is a transcription factor linked to the circadian rhythm which has been identified as a candidate gene to type 1 diabetes. Amongst the genes regulated by this transcription factor there is a strong candidate gene: the Interleukin 21, responsible of the proliferation of the T CD4+ lymphocyte, contributing to the destruction of the β cells in the pancreas during type 1 diabetes. My thesis project consisted on studying how the NOD and C3H alleles of Arntl2 control the expression of Il-21 and how it affected the immune system. The analysis of the immune cells revealed that the mice with a C3H allele in Idd6.3 produce less CD4+, CD8+ and CD4+IL-21+ T cells than the mice with a NOD allele in Idd6.3 and the NOD.B6 Arntl2-/-. We showed that this difference is due to the fact that ARNTL2 binds specifically to the RNA POL II binding site on the Il-21 promoter and inhibits its expression. We also have shown that a Knockout of this gene increase the apoptosis resistance of the thymocytes. And that this resistance was due to IL-21, indeed, injections of IL-21 brought the same increase in resistance than the one in the strains without a functional version of Arntl2. These new results show an unexpected role for Arntl2 in the regulation of the immune equilibrium by its control of Il-21 expression, and in the thymic selection of T cell by apoptosis
Hassainya, Yousra. "Identification d'épitopes T-CD8+ HLA-A2 restreints issus de la proinsuline par une stratégie d'immunologie inverse, et évidences pour une nouvelle voie d'apprêtage cytoplasmique." Paris 5, 2005. http://www.theses.fr/2005PA05N05S.
Type I diabetes is an autoimmune disease caused by specific destruction of beta cells of patients pancreas ' Langerhans islets. CD4 T cells and CD8 T cells are the major implicated cells. A lot of studies were reported concerning CD4 T cells. Inversaly only few studies were focalized on CD8 T cells despites some concluding reports. Therefore we decided, to study this CD8 T cells compartment by applying a reverse immunology strategy combining in vitro digestions of the proinsulin by the proteasome, using of two algorithms to predict affinity for HLA-A2 molecules and in vitro measuring of these affinities for selected peptides. We have identified six proinsulin epitopes HLA-A2 restricted. Moreover, interesting resuts allows us to study a more global question concerning proinsulin degradation and we have identified a new cytoplasmic processing pathway for class I epitopes
Hirtz, Christophe. "Intérêt diagnostique et clinique de la protéomique salivaire : étude préliminaire du diabète de type 1." Montpellier 1, 2005. http://www.theses.fr/2005MON12200.
Crouigneau, Roxane. "Nouvelles microcapsules fonctionnalisées et standardisées : Application à la thérapie cellulaire du diabète de type 1." Thesis, Université Grenoble Alpes (ComUE), 2019. http://www.theses.fr/2019GREAS033.
Cell therapy with allogenic pancreatic islets is a treatment used for type 1 diabetic patients for whom the usual insulin treatments does not work anymore. However, this therapy requires administration of an immunosuppressive treatment, that leads to many side effects and complications. The implantation of microencapsulated islets that become stealth to the host’s immune system consists in an alternative to immunosuppressive treatments. This technique presents very promising results in several clinical trials, but there are still many challenges that need to be tackled, to increase the durability of a functional graft. The FUTURCAPS project, in which this PhD is integrated, focused on improving two currently limiting points : the properties of the polymers used for the encapsulation, by using chemically modified alginates, that increase the mechanical stability of the capsules ; and the control in size and shape of the capsules, that enables to have an optimal diffusion barrier, by using a microfluidics flow focusing (MFFD) droplet generation system, developed at the CEA (Grenoble). To do this, the physicochemical properties of the different alginates were first characterized, and theoretical rheological models that define their behaviour were determined. Then, the parameters involved in the formation and gelation of the droplets were studied (viscosity, surface tension, contact angle, shear rate while forming the droplets, and gelation rate). Following these studies, monodisperse capsules (variation coefficients under 5 %) were obtained in microfluidics with the different alginates (that have very diverse properties), and these latter were characterized in terms of size, shape and permeability. Eventually, neo-natal pig, and human pancreatic islets were encapsulated in the alginates studied. The encapsulated islets viability was measured in vitro, and they have also been implanted in mice, in order to check for biotolerability and viability in vivo after 15 days
Griseri, Thibault. "Rôle immunorégulateur des lymphocytes TNK dans le diabète de type 1 et les infections virales." Paris 5, 2006. http://www.theses.fr/2006PA05N24S.
Invariant natural killer T (iNKT) cells can prevent type 1 diabetes by impairing T cell responses to pancreatic β cells. As iNKT cells can also promote T cell responses to pathogens, and as viruses can trigger autoimmune diabetes, we investigated the effect of iNKT cells on virus-induced diabetes. Mice expressing the lymphochoriomeningitis virus (LCMV) nucleoprotein (NP) in their pancreatic β cells develop diabetes after LCMV infection. Here, we show that although iNKT cells promote systemic anti-LCMV CD8 T cell responses, theyn also completely abolish LCMV-induced diabetes. Locally in the pancreas, iNKT cells induced the production of large amount of antiviral cytokines inhibiting LCMV replication
Favennec, Marie. "Etude de la voie des kynurénines dans l'obésité humaine." Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S037/document.
Tryptophan, an essential amino acid, is either used in protein synthesis or metabolized via the serotonin or the kynurenine pathway. The kynurenine pathway is the main route of tryptophan degradation and generates several metabolites collectively called “kynurenines”. The expression of kynurenine pathway enzymes is induced by inflammatory mediators. Consequently kynurenine synthesis could be induced in individuals with obesity. In fact, obesity is characterized by a chronic low grade inflammation of the adipose tissue reflected by increased serum levels of inflammatory factors which are known to contribute to the development of obesity-induced insulino-resistance. Some metabolites of the kynurenine pathway have been proposed to be risk factors for the development of insulin resistance. Bariatric surgery is currently the most effective treatment for severe obesity and results in a significant weight loss, a decreased level of inflammatory factors and an amelioration of glucose homeostasis. The first enzyme of the kynurenine pathway, IDO1, is known to be more expressed in the adipose tissue of individuals with obesity compared to lean individuals. The kynurenine over tryptophan ratio reflects the activity of IDO1 and is also increased in individuals with obesity.Our objective was to characterize the expression of the kynurenine pathway enzymes in the adipose tissue of women with severe obesity and to evaluate serum levels of the kynurenine pathway metabolites to determine whether these factors could be associated with the appearance of diabetes. This study was performed in women with severe obesity with or without type 2 diabetes. Then we investigated the consequences of weight loss induced by bariatric surgery on levels of circulating kynurenines in order to evaluate whether these variations could explain the improvement in glucose control and type 2 diabetes remission after one year follow-up.In this study, we have shown that several kynurenine pathway enzymes were more expressed in the adipose tissue of women with obesity compared to lean controls. This increase is due to the presence of pro-inflammatory macrophages in the adipose tissue and also comes from the adipocyte response to inflammatory stimuli. In addition, we observed that the serum level of kynurenine and kynurenine over tryptophan ratio are higher in women with higher BMI and they both decrease one year after bariatric surgery. In addition, we observed that the serum level of kynurenine and kynurenine over tryptophan ratio are higher in women with higher BMI and they both decrease one year after bariatric surgery. As expected, bariatric surgery is associated with the improvement and even the remission of type 2 diabetes. We have shown that higher levels of kynurenic acid and quinolinic acid one year after the surgery are associated respectively with type 2 diabetes remission and better glucose homeostasis and that lower levels of xanthurenic acid are associated with better glucose homeostasis
Poumeyrol, Stéphanie. "Empreintes du corps malade sur le corps féminin à l'adolescence : l'exemple du diabète insulino-dépendant : Étude clinique et projective." Paris 5, 2009. http://www.theses.fr/2009PA05H020.
Our research concerns the feminisme adolescence process of subjects with diabetes mellitus type-1 in order to reintroduce-which seems essential to us- the theme of the sexual difference in illness. Our approach leaves the question of the origin of the desease unresolved in order tu study which elements facilitate its integration and the access to the psychic autonomy of girls affected by this chronic disease. Beyond the heritage of the sick and dependant body, how can these subjects manage through the reappropriation of their pubescent body? This question leads us to the notions of masochistics liaison and passivity (which is, according essential in our population but also in the suffering body as of integration of the libidinal body. The clinical illustrations of 20 adolescents aged 12-17 with diabetes mellitus type-1 allows us to identify elements of a common dynamic between "the disease work" (J-L Pedinelli) and female sexual identification (described by J. Schaeffer). Furthermore, noncompliance with treatment- common behaviors in this population- appear as many attempts of reappropriation of the dependent body: masochistic behaviors allows the physical appropriation of pulsionnal pressure, but it is always running the risk of this own racing when the propping up of the object comes to miss or cannot be accepted
Kared, Hassen. "Facteurs de croissance et progéniteurs hématopoïetiques autologues : de nouveaux outils pour la restauration de la tolérance au soi dans le diabète auto-immun." Paris 5, 2006. http://www.theses.fr/2006PA05D036.
Expansion of regulatory T cells in vivo is a promising strategy to cure auto-immune diseases. Here we demonstrate that stimulation of hematopoiesis either by the growth factor G-CSF or by transplantation of mobilised hematopoietic progenitors (HPC), but not of medullary hematopoietic stem cells, increases CD4+CD25+Foxp3+ regulatory T cell (Treg) numbers in peripancreatic lymph nodes and provides protection against type 1 diabetes in the NOD mouse. Protection is based on the following mechanisms : G-CSF promotes the differentiation of semi-mature plasmacytoid dendritic cells which in turn recruit Treg whereas HPC directly expand Treg. The HPC-Treg interaction requires cell contact and activates the Notch signalling pathway via Jagged2, selectively expressed on HPC, which increases Notch3 expression on Treg. This selective expression of jagged2 on mobilised progenitors needs to be confirmed in human and could represent a novel way to distinguish immunogenic from tolerogenic progenitors
Arapis, Konstantinos. "Mise au point de modèles précliniques de chirurgie bariatrique chez le rat rendu obèse par un régime hyperlipidique." Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCC086.
Sanyoura, May. "Contributions monogéniques dans le diabète insulino-dépendant au Liban." Paris 7, 2013. http://www.theses.fr/2013PA077112.
Diabetes mellitus represents a heterogeneous group of metabolic disorders characterized by sustained high blood glucose concentrations. Disease etiology is still poorly understood but involves both genetic and environmental factors. The main aim of this thesis was to identify and study genes responsible for monogenic forms of juvenile-onset insulin-dependent diabetes (JOD) in the Lebanese population. Due to the high rate of consanguinity and intra-population endogamy, the Lebanese population is particularly well suited to address the question of the responsibility of monogenic contribution to JOD. Using a family-based genetic study, we identified evidence of linkage near the WFS1 gene, responsible for Wolfram syndrome. We identified one frameshift mutation, the WFS1LIB mutation, which was associated with a delayed onset of optic atrophy (OA). The delayed onset of OA in WFS1LIB homozygous patients was family dependent and suggested the role of a modifier variant. Our results suggest that one common variant located in the 5' regulatory region of the WFS1 gene is associated with delayed onset of OA and decreased expression of WFSL After excluding ail genetically explained families, we identified evidence of linkage on chromosome 11. We selected the most plausible candidate gene and identified 3 mutations. We then used a siRNA-mediated knockdown approach in dispersed islets, INS-1E, and purified bêta cells and showed that gene deficiency resulted in increased cell death and decreased insulin expression. The last study concerns the genetic investigation of a diabetic Lebanese patient initially diagnosed as Wolfram Syndrome. Using linkage study and sequencing, we selected ALMS1, responsible for Alström Syndrome, in which we identified a novel splice mutation. In conclusion, monogenic forms of diabetes are likely to represent a significant subset of JOD cases, generally diagnosed as T1D, particularly in highly consanguineous populations such as Lebanon
Naudin, David. "Importance des Fonctions exécutives dans l’observance thérapeutique chez les patients présentant un diabète de type 1." Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCD003.
The announcement of a chronic pathology exposes the patient to a double learning process involving the self-management of his/her pathology and treatment, but also the establishment of a new relationship with him/herself. In addition to disease’s acceptance, to renunciations and hardships, the patient makes additional efforts to learn and acquire new skills and to maintain them over time. Through patient education, the patient sets goals and objectives that are negotiated with health care providers. The exercise of developing but also evaluating goals and objectives presupposes that the patient becomes aware of his/her own functioning and can observe his/her conduct through self-observation. This self-observation or reflexivity allows the patient to make decisions. He/she will also be able to adjust or change them during their implementation. The preparation, control and execution of the action presupposes therefore an evaluation of the ongoing action and its obtained, or potential, results. The objective of this thesis is to characterize the mechanisms underlying the process of transition to therapeutic action in patients with type 1 diabetes. The theoretical framework is based on executive functions and known mechanisms of patient’s adherence. These results should include practical proposals and a revisit of diabetes patient education programs
Scuotto, Angelo. "Contribution à l’étude des agrégats bifides : sélection, caractérisation, mécanisme et prévention du diabète de type 1." Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S014/document.
Some bifidobacterial strains are used to ferment infant formulas. Their properties (modulation of microbiome, regulation of bacterial translocation, dendritic cells maturation) are related to their ability to secrete high molecular weight compounds during the bacterial fermentation. The first objective of the study was to characterize the molecules secreted by the strain B.breve C50 used as a reference, and to determine whether other bifidobacteria can secrete molecules with similar properties. Analysis using gas chromatography (GC), mass spectrometry (MS), electrophoresis, protein sequencing showed that the B.breve C50 fermentation compounds are constituted of aggregates (>600kDa) combining units of a cell wall lipoprotein with a CHAP domain and sugars moities, mostly glucose. The aggregates are recognized by TLR6, indicating that the protein was diacetylated. They are also ligand of the galectin 1, suggesting that the hexosamine and galactose moieties detected by GC surrounded the aggregates. In silico analysis showed that a B.longum gene exhibiting a high homology with the B.breve C50 gene, coded for a lipoprotein, which was secreted during fermentation, and formed aggregates with sugars. B.bifidum species likely does not secrete similar aggregates since the sequence of the homologous gene is deprived of lipobox. B.longum CBi0703 and B.breve C50 aggregates shared the same global structure (lipoproteins with CHAP domain bordered by sugars primarily constituted of glucose and mannose). Remarkably, the CBi0703 aggregates were also able to bind Gal-1 but were lacking binding capacities to TLR6. It is likely that the hydrophobicity of the protein sequence, as well as the lipid and sugar compositions prevented the recognition of the lipoprotein structure by the TLR6 receptor. Secondly, a putative phagocytosis of aggregates was investigated. Fluorescent-labeled aggregates are not detected within cells after direct contact (ex-vivo) or oral challenge in animals (in vivo). Capture of the aggregates by antigen presenting cells seemed improbable. The two types of aggregates being recognized by galectin-1, regulation of the intestinal bacterial translocation by the aggregates likely involves the hexosamines and galactose surrounding their surface. In a third step, the possible involvement of the bifidobacterial aggregates in the prevention of type 1 diabetes was investigated. Actually, breast milk was previously shown to prevent diabetes onset in old NOD mice. Detection of bifidobacteria using amplification of the gene encoding the B.longum lipoprotein was positive in 21 human milk samples out of 31 (i.e. 12 mothers out of 16). Conversely, B.breve is rarely isolated (2/16 mothers). Since transcriptomic analysis showed that the lipoproteins were continuously synthesized, we hypothesized that the bifidobacterial aggregates were secreted by the bifidobacteria harbored in human milk. To ensure that B.longum aggregates play a role in the protection induced by human milk, they were assayed at an anti-inflammatory dose. Contrary to breast milk which reduced the incidence of T1D in NOD mice older than 18 weeks (p <0.001), only early but not persistent protection is observed during bifidobacterial aggregates intake. The protective effect was observed in the absence of intestinal bifidobacteria. Variation in intestinal bacterial colonization did not match in groups drinking human milk or bifidobacterial aggregates at an inflammatory dose. The difference in kinetics could support the delay in diabetes onset induced by the bifidobacterial aggregates
Rouxel, Ophélie. "Rôles des cellules MAIT (Mucosal Associated Invariant T) dans la physiopathologie du diabète de type 1." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB114.
Type 1 diabetes (T1D) is an auto-immune disease characterized by the selective destruction of pancreatic islet β cells resulting in hyperglycemia and requiring a life-long insulin replacement therapy. The physiopathology of T1D is complex and still not entirely understood. Both innate and adaptive immune cells are involved in the pathogenesis and the regulation of T1D. While diabetes development can clearly be associated with genetic inheritance, environmental factors were also implicated in this autoimmune diseases. Recent studies have highlighted the role of the intestinal microbiota in the development or protection against T1D. Gut microbiota analyses in patients have shown differences before the onset of T1D. Moreover, several studies also described gut mucosa alterations in NOD mice and in T1D patients. MAIT (Mucosal Associated Invariant T) cells are innate-like T cells recognizing the MR1 molecule and expressing a semi-invariant receptor Vα chain (Vα7.2-Jα33 and Vα19-Jα33 in mice). MAIT cells are activated by bacterial metabolites, derived from the synthesis of riboflavin. Their particularity is to rapidly produce various cytokines such as TNF-α IFN-γ, IL-17 and granzyme B. The localization and the function of MAIT cells suggest that they could exert a key role in the maintenance of gut integrity, thereby controlling the development of autoimmune responses against pancreatic β cells. To summarize, our results in T1D patients and in NOD mice indicate an abnormal MAIT cell activation in this pathology, which occurs before disease onset. The analysis of peripheral tissues from NOD mice highlights the role of MAIT cells in two tissues, the pancreas and the gut mucosa. In the pancreas, MAIT cells frequency is elevated and they could participate to the β cells death. In contrast to the pancreas, in the gut mucosa MAIT cells could play a protective role through their cytokines production of IL-22 and IL-17. Our data in Mr1-/- NOD mice, lacking MAIT cells, reveal that these cells play a protective role against diabetes development and in the maintenance of gut mucosa integrity. Moreover, the presence of gut alteration as T1D progress in NOD mice underscores the importance of MAIT cells in maintaining gut mucosa homeostasis. Interestingly, MAIT cells could represent a new biomarker towards T1D progression and open new avenues for innovative therapeutic strategies based on their local triggering
Hammoud, Laika Taghrid. "Immunogénicité de la préproinsuline dans le diabète de type 1 humain chez un modèle murin humanisé HLA." Paris 5, 2008. http://www.theses.fr/2008PA05T022.
Type 1 diabetes involves the activation of lymphocytes against p cell autoantigens. In animal models, the predominant role of T lymphocytes is supported by experiments in which diabetes is transferred into naive recipients by diabetogenic T cells, is prevented by antibodies that interfere with T lymphocyte activation or fails to develop in diabetes-prone mice in which key genes in T lymphocyte differentiation or activation are non functional. In man, T lymphocytes are predominant within insulitis at early stages of diabetes. Occurrence of diabetes in an immuno-deficient patient deprived of B lymphocytes further underscores the role of T lymphocytes in human diabetes. MHC class II-restricted CD4+ T cells are central in the autoimmune diabetes process but CDS* T cells play a pivotal role in its initiation in NOD mice. In the human, CD8+ T cells are predominant in the islet cell infiltrate of acutely diabetic patients in most observations. Recurrent diabetes in recipients of isografts from a discordant twin is accompanied by predominant CD8+ T cell infiltration. Among p cell autoantigens, proinsulin has been ascribed a key role in diabetes. In man, insulin and proinsulin are common targets of autoantibodies and T cells in diabetic and prediabetic individuals. Anti-insulin antibodies (IAA) are the first to be detected in children at risk for diabetes and carry a high positive predictive value for diabetes in siblings of type 1 diabetic patients. In NOD mice, injection of insulin-specific T cell clones accelerate diabetes. Protection from diabetes is obtained by injecting insulin in prediabetic mice. In addition, proinsulin 1"'" or 2"'" NOD mice show delayed or accelerated diabetes, respectively. We and others have obtained evidence that a restricted region of human proinsulin located in the B chain and adjacent C-peptide clusters proteasotne cleavage sites generating correct C-termini of putative MHC class 1 peptides and a high number of epitopes that are recognized by diabetic CDS* T cells. Other epitopes have been located within the A chain. Recognition of epitopes that are located within the C peptide and C peptide-B chain junction including residues that are excised during the insulin secretion process makes a strong case for proinsulin as an autoantigen in diabetes. However, there has been no study of epitopes located within the preproinsulin leader sequence despite strong evidence that leader sequence peptides can be presented by class I HLA molecules, especially HLA-A2. 1. To characterize class I-restricted epitopes within the preproinsulin leader sequence, we selected 8- to 11-mer peptides carrying anchoring residues for class I molecules. These peptides were studied for binding to common class I molecules and for carrying C-terminal residues generated by proteasome digestion. HLA-A2-restricted peptides were further tested for immunogenicity in HLA-A*0201 transgenic mice. Peptides were studied for recognition by PBMCs from diabetic patients. To study the natural processing of preproinsulin leader peptide, mouse CD8+ T cell clones specific to HLA-A*0201 -restricted peptides were tested for cytotoxicity against PS 15 cells transfected with the HHD and preproinsulin genes
Kikkas, Ingrid. "Development of immunoassays for diagnosis of type 1 diabetes." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA114824.
Type 1 diabetes is an autoimmune disease characterized by the destruction of pancreatic beta cells within the islets of Langerhans. In the course of this autoimmune process, autoantibodies are generated against several beta-cell antigens, e.g. insulin, glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA-2) and zinc transporter 8 (ZnT8). At least one autoantibody against one of these antigens is present in >95% of individuals with type 1 diabetes upon hyperglycemia detection. These autoantibodies can serve as early markers of type 1 diabetes, since they can be present years before disease onset, allowing for an early diagnosis before clinical manifestations. In the course of this thesis we have developed, in partnership with a clinical research team, a series of original diagnostic tests, based on the early detection of the different anti-Langerhans islet autoantibodies from human serum samples. These diagnostic tests include bridging ELISAs for the detection of autoantibodies to insulin, IA-2 and GAD65, which are rapid, non-radioactive and easy-to-use. Moreover, a lateral flow immunoassay (dipstick) for detection of autoantibodies to IA-2 was developed. The key advantage of lateral flow immunoassay is its user-friendly format: results can be obtained within 45 min using very small volumes of sera and without the use of any specialized apparatus. All these in-house assays were validated with diabetic and healthy human serum samples and the assay performances were compared to commercially available tests on the market. In addition, we have developed a multiplex assay for simultaneous detection of multiple diabetes-associated autoantibodies, which is time-effective and increases the diagnostic and predictive values of the assay, comparing to single autoantibody detection. This multiplex assay was validated for detection of two autoantibodies i.e. IA-2A and GADA and compared to in-house IA-2A and GADA bridging ELISAs
Brossaud, Julie. "Modulation pré et post-récepteur de l’exposition aux glucocorticoïdes : rôles du diabète de type 1 et de la vitamine A." Thesis, Bordeaux 2, 2013. http://www.theses.fr/2013BOR22081/document.
Rôles to mobilize body resources and to adapt to endogenous or exogenous changes that might disrupt the homeostasis of the body. Nutritional & metabolic factors may modify the intensity of GC action in: i) the activation of the corticotrope axis and their secretion by the adrenals, ii) their bioavailability ("pre-receptor" regulation), iii) the transcriptional activation of their receptors ("post-receptor" regulation). The main target of this work is to explore the role of some metabolic/nutritional endogenous or exogenous factors in modulating pre- and post-receptor action of GC. Our attention first focused on the role of diabetes and the related inflammation in patients with type I diabetes, and pre-receptor metabolism of cortisol. We showed that a significant increase in the activity of hydroxysteroid dehydrogenase 1, the main enzyme of intracellular cortisol regeneration, is correlated with markers of inflammation in diabetic children. This suggests a link between diabetes and the low-level chronic inflammation and increased cellular exposure to GC . Then, we focused on the action of all-trans retinoic acid (atRA), the active metabolite of vitamin A on the transcriptional activity of GC. We used an in vitro model of hippocampal cells as GC and atRA have contrasted effects on mnesic processes in vivo. We observed a transcriptional interaction between the GC and retinoic pathways targeting their receptors and genes involved in neuronal plasticity. atRA also affects the phosphorylation of the GC receptor and modifies its transcriptional activity. Lastly, both atRA and GC affect cellular organisation of actin cytoskeleton. The knowledge acquired by studying the action of nutritional molecules on GC action could be used to easily reduce the deleterious effects of GC in chronic stress. Clinical studies have started in this direction
Gauvrit, Anne. "Étude de l'implication des lymphocytes T CD8 dans la physiopathogénie du diabète de type 1(T1D), chez la souris NOD (Non Obese Diabetic)." Nantes, 2003. http://www.theses.fr/2003NANT2024.
Gouty-Dufayet, de La Tour Dominique. "Na,K-ATPase et diabète : facteurs génétiques et environnementaux." Aix-Marseille 2, 1998. http://theses.univ-amu.fr.lama.univ-amu.fr/1998AIX2666U.pdf.
Bélanger, Alexandre. "Analyse des effets comportementaux du diabète de type II chez des rats de souche Zucker (ZDF)." Thèse, Université du Québec à Trois-Rivières, 2003. http://depot-e.uqtr.ca/4003/1/000102880.pdf.
Carpentier, Joëlle. "Déterminants de la pratique d'activité physique chez les adultes québécois attteints du diabète de type 2." Thèse, Université du Québec à Trois-Rivières, 2014. http://depot-e.uqtr.ca/7336/1/030673395.pdf.
Vantyghem, Marie-Christine. "Allogreffe intraportable d'ilôts pancréatiques endocrines dans le diabète de type I : aspects qualitatifs et quantitatifs de l'isolement ; résultats cliniques préliminaires." Lille 2, 2000. http://www.theses.fr/2000LIL2MT14.
Diouri, Omar. "Automatisation de la perfusion continue ambulatoire d'insuline visant la normalisation glycémique dans le diabète de type 1 : développements pour améliorer le contrôle postprandial." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT019/document.
Carbohydrates (carb) and bolus counting is a therapeutic method used in type 1 diabetes (TD1) which aims to adapt insulin treatment to patient own way of life. It is based on patient’s autonomy since they are allowed to eat any type of food on the condition to adapt insulin doses to the meal ingested. Patients receive a medical education to implement this method, but still carb counting remains a hard task and boluses are frequently erroneous.Thanks to smartphone technical capacities, many applications replacing paper documents and booklets aiming at helping patients in these daily tasks have been developed. But very few studies were conduced to evaluate them clinically.After an overview of the common tools used by TD1 patients to count carbs , we will see the main mobile applications available to help patient in carb counting and bolus estimation. We will then discuss the few clinical studies conduced on those apps.We will finally present an original android application called GLUCAL and developed by the diabetology team of the University Hospital of Montpellier (France). This tool was tested during two clinical studies. A preliminary study has been conduced before a randomized cross-over study which is the first one performed on such an application.This work will help to evaluate the role of GLUCAL in improving carb counting and reducing mistakes of bolus calculation. It will also assess the performance of the application on patient’s glycaemic control
Blouin, Valérie. "Les apports alimentaires des enfants diabétiques de type 1, selon leur plan d'alimentation et leur insulinothérapie." Thesis, Université Laval, 2011. http://www.theses.ulaval.ca/2011/27975/27975.pdf.
Hartemann-Heurtier, Agnès. "Définition des sous-populations lymphocytaires T impliquées dans la pathogénie du diabète de type 1 : nouvelles opportunités thérapeutiques." Paris 5, 2003. http://www.theses.fr/2003PA05N047.
Grasset, Estelle. "Mécanismes moléculaires régulant l'action du glucagon-like peptide one dans la physiopathologie du diabète de type 2." Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30301/document.
According to the World Health Organisation, Type II Diabetes, characterized by an alteration of glycemic control, causes numerous death around the world. After a meal, gut secretes Glucagon-Like Peptide one (GLP-1) which regulates glycemia by stimulation of insulin secretion and inhibition of gastric emptying and food intake. Although GLP-1 acts as an endocrine hormone on its target organs through the GLP1 receptor, its action is mainly mediated by nervous pathway involving vagus nerve and gut-brain-periphery axis. Thus, GLP-1 based therapies are used to control glycaemia in type 2 diabetic patients, but, efficiency of the treatment is heterogeneous defining a state of GLP-1 unresponsiveness. Molecular mechanisms involved in this unresponsiveness are not known but could be linked to the changes in gut microbiota (dysbiosis), key element in the development of metabolic diseases. We first found that diabetic mice (high fat diet) are unresponsive to hypoglycemic action of GLP-1 and present enteric neuropathy, impaired gut-brain axis and reduction of GLP-1r and neuronal NO synthase expression in the ileum. In addition, GLP-1-induced nitric oxide production in primary neuron culture is decreased. These effects were also found in germ-free or antibiotic-treated mice under normal chow diet, indicating the involvement of gut microbiota. By contrast, high fat diet mice treated with antibiotics show an improvement of GLP-1 action. This gut incretin action could also depend on the circadian cycle for which we observed a wavering of insulin secretion, GLP-1r expression and gut microbiota. Moreover, the GLP-1 response of control mice is better in the day than in the night and the different mice model resistant to GLP-1 (HFD, axenic or antibiotics) present the same marked variations in the expression of major clock genes. Overall our results show that in type 2 diabetes GLP-1 action is lowered and can be explained by decreased neuronal expression of GLP-1r as well as the NO-dependent signaling pathway regulating insulin secretion induced by GLP-1. Microbiota or the circadian clock seems essential in this GLP-1 sensitivity
Boubenna, Nacer. "Modulation of the immuno-metabolism axis in type-1 diabetes." Thesis, Aix-Marseille 2, 2010. http://www.theses.fr/2010AIX22065.
In this thesis we sought to understand the link between metabolic deregulation and immune deregulation in the context of the NOD mouse autoimmune model. We observed that bezafibrates protect NOD mice from type 1 diabetes (T1D). We showed that pancreas beta islet infiltration by lymphocytes and APCs was diminished. IL-6 decrease in bezafibrate treated mice serum suggested a general dampening down of inflammation. Besides we evaluated the effect of bezafibrate out of the immune system by using a low-dose streptozotocin method and we observed that bezafibrate mice treated were protected. In a second part of this study we observed an overexpression of Toll-like receptors (TLR) 1, 2, 6 in NOD mice compared to C57BL/6 controls. This was noticeable at the transcription and translation level. We showed that this overexpression had a functional role. Indeed APCs from NODs secreted more IL-6, and B cells secreted more IgM when stimulated with corresponding ligands. We then modified the lipid content of NOD mice by using bezafibrates to decrease lipidemia, and a high fat diet (HFD) to increase lipidemia. No modulation of TLR2 and TLR6 expression was observed. However, APCs from HFD mice were more susceptible to TLR2/6 ligand FSL-1 stimulation by secreting more IL-6 than control or bezafibrate treated NODs. We here highlight the important links existing between metabolism immunity in the autoimmune T1D onset
Grela, Françoise. "Modulation de la réponse immunitaire par TLR7: rôle dans le diabète de type 1 et l'asthme allergique." Phd thesis, Université René Descartes - Paris V, 2008. http://tel.archives-ouvertes.fr/tel-00322355.