Letteratura scientifica selezionata sul tema "Diabète non-insulinodépendant – Génétique"
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Articoli di riviste sul tema "Diabète non-insulinodépendant – Génétique":
Froguel, P., N. Vionnet, D. Gauguier, M. Vaxillaire, H. Zouali, P. Passa e G. Velho. "Génétique du diabète non insulinodépendant". médecine/sciences 10, n. 8-9 (1994): 795. http://dx.doi.org/10.4267/10608/2714.
Dubois-Laforgue, D., S. Caillat-Zucman, E. Larger, I. Djilali-Saiah, A. Mercadier, R. Assan, C. Boitard e J. Timsit. "Diagnostic génétique de l'hémochromatose primitive par recherche de la mutation C282Y du gène HLA-H. Application au diabète non insulinodépendant". La Revue de Médecine Interne 18 (maggio 1997): s111—s112. http://dx.doi.org/10.1016/s0248-8663(97)80328-1.
Tesi sul tema "Diabète non-insulinodépendant – Génétique":
Andreelli, Fabrizio. "Régulation de l'expression des gènes in vivo chez l'homme". Lyon 1, 2001. http://www.theses.fr/2001LYO1T092.
Aït, 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.
Dina, Christian. "Analyse d'association génome entier de 3 pathologies : le diabète de type 2, le syndrome de Brugada et le prolapsus valvulaire mitral : observations sur l'architecture génétique de traits complexes". Nantes, 2012. http://archive.bu.univ-nantes.fr/pollux/show.action?id=d029660f-aac0-4e98-ad6a-35894eef4403.
The escalating prevalence of cardio-vascular and metabolic disorders, and the limitations of currently available preventive and therapeutic options are increasingly important factors reducing the quality and life expectancy resulting in a dramatic increase in public spending in the health field. This emergency highlights the need for a more complete understanding of the pathogenesis of these diseases as well as the need for bio-markers to increase their predictability is a priority. The genetic approach, in this context, is among the most promising strategies. This approach has many variants. One of the most popular in the last decade is the approach of genome-wide association studies. The strategy is based on the assumption of an important role played by common genetic variants for common diseases. This paradigm has been called the assumption of "common variant, common disease". As part of my thesis, I explored the effect of common variants in three diseases, Diabetes Type 2, Mitral Valvular Prolapse, both being common pathologies and the Brugada syndrome, which is rare in the population. These three diseases strongly contribute to the explosion of population health needs, either by the severity of complications for Type 2 Diabetes, through the need of major surgery for Mitral Valvular Prolapse and through the increased risk of Sudden Death for Brugada Syndrome. I applied various techniques such as genetic imputation, meta-analysis and correction of stratification to help highlight their genetic bases. In Type 2 diabetes, highlighting of the genetic architecture was already well advanced and I participated in the deepening of knowledge. This work helped identify up to 40 genes. We have also shown that there is a substantial polygenic component underlying the genetic architecture of this disease and that most of the identified genes point to a dysfunction of beta cells. Studies on Mitral Valvular Prolapse are less advanced. I selected genetic variants showing a possible association and these variants are being replicated. Preliminary results on the Framingham study showed the possible involvement of genes of the extracellular matrix. Finally, for Brugada Syndrome, I clearly identified three loci that show a highly significant association with the disease. These loci were replicated as well in a European population in Japanese population. If the involvement of genes coding for ion channel proteins (SCN5A and SCN10A) seems to be confirmed, strengthening the definition of Brugada Syndrome as a channelopathy, another pathway possibly related to cardiac development was also identified (through the gene HEY2). Finally, during my PhD, I also contributed to create the concept of common variant for rare disease (CV/CR)
Auboeuf, Didier. "Recherche des mécanismes transcriptionnels impliqués dans les anomalies de l'expression de gènes dans le tissu adipeux chez les sujets diabétiques de type 2". Lyon 1, 1998. http://www.theses.fr/1998LYO1T147.
Dance, Arnaud. "Exploration du rôle du récepteur purinergique P2RY1 dans le risque et la physiopathologie du diabète de type 2 : perspectives de la génomique fonctionnelle humaine". Electronic Thesis or Diss., Université de Lille (2022-....), 2023. http://www.theses.fr/2023ULILS072.
Genome-wide association studies (GWAS) have shown that the P2RY1 locus is associated with type 2 diabetes (T2D) risk and with glucose levels. P2RY1 is a G-protein coupled receptor (GPCR) activated by ATP and ADP, which is highly expressed in pancreatic islets, particularly in β cells where, ATP/ADP stimulate insulin secretion by activating the ATP-dependent potassium channels. Through functional genetics, we aimed to analyze the putative contributions of genetic variants of P2RY1 to T2D risk and to other metabolic traits. We then characterized the downstream signaling pathways of P2RY1 in human pancreatic beta cells and deciphered its putative role in insulin secretion.P2YR1 was sequenced in 9,266 adults including cases with T2D and normal glucose controls. To assess the functional effect of each identified variant, we performed 1) luciferase assays (NFAT-RE system) on HEK293 cells overexpressing each variant, followed by P2YR1 activation by increasing doses of MRS2365 (methanocarba-2MeSADP) that is a specific agonist of P2RY1, and 2) immunofluorescence to assess cellular localization and expression of each mutant. We also performed expression quantitative trait loci (eQTL) analysis in 103 donors based on RNA-seq of pancreatic islets and DNA microrrays genotyping. In human pancreatic β cells (EndoCBH5), we performed glucose-stimulated insulin secretion (GSIS) assays coupled to P2YR1 activation by MRS2365 or inhibition by MRS2500.We identified 22 rare missense variants in P2RY1 (including 10 novel variants). Our in vitro analyses highlighted 7 loss-of-function mutations. 87% of the mutation carriers presented with T2D. Expression QTL analyses showed that a block of single nucleotide polymorphisms (SNPs; n=63) located in an enhancer of human islets was significantly associated with increased islet expression of P2RY1 and decreased T2D risk while another block of SNPs (n=51) was significantly associated with decreased expression of P2RY1 in human islets and increased T2D risk. In EndoCBH5, the GSIS assay showed that the P2RY1 specific agonist MRS2365 led to a 30% increase of insulin secretion when stimulated with 20mM of glucose. A kinome analysis (through PAMGENE technology) and transcriptomic analysis (through RNA sequencing) of the P2RY1 pathway in the EndoCBH5 cells in response to MRS2365 agonist orevealed that the activation of P2RY1 led to a decrease in the expression of TXNIP.Our genetic, functional genomic and pharamacological studies suggest that P2RY1 dysfunction is causatively associated with T2D riskand that P2RY1 contributes to the activation of the insulin secretion pathway. P2RY1 potent and selective agonists that cannot cross the blood-brain barrier are available, and could be tested as a potential new class of insulin secretagogues
Diedisheim, Marc. "Dédifférenciation de la cellule bêta pancréatique humaine". Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB074/document.
Clinical and experimental evidences indicate a reduced functional β cell mass in type 2 diabetes. A recent hypothesis implicates β cell dedifferentiation in this reduction of functional β-cell mass. The vast majority of data related to β cell dedifferentiation derive from rodent models, and only indirect evidences are available in human. Our goal was to model human β-cell dedifferentiation using the functional human pancreatic β-cell line, EndoC-βH1, and primary human pancreatic islets. By screening a number of molecules in EndoC-βH1 cells, we found that FGF2 treatment dramatically reduces insulin production and MAFA expression, a β cell specific transcriptional activator. RNASeq of EndoC-βH1 cells treated with FGF2 revealed the down-regulation of additional human β cell specific markers, including INS, MAFB, SLC2A2, SLC30A8 and GCK. In parallel, FGF2 treatment activated the expression of β cell disallowed genes. This is the case for transcription factors such as MYC, HES1, SOX9 and NEUROG3. This is also the case for hormones such as GASTRIN and PYY. Such data were further confirmed by qPCR and immunostaining on primary human islets, attesting that dedifferentiation process occurs in human primary β cells. FGF2-induced dedifferentiation was time- and dose-dependent, and reversible upon wash-out. Furthermore, transcriptomic analysis revealed an increase of TNFRSF11B (osteoprotegerin) expression upon FGF2 treatment. TNFRSF11B is a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL). Our experimental data on EndoC-βH1 demonstrated that FGF2-induced TNFRSF11B protected β cells against TNFSF11 (RANKL) signaling by preventing P38 phosphorylation. Finally, analyses of transcriptomic data revealed increased FGF2 mRNA levels in ductal, endothelial and stellate cells in pancreases from type 2 diabetic patients, whereas FGFR1, SOX9 and HES1 mRNA levels increased in islets from type 2 diabetic patients. In conclusion, we developed a robust model to study β-cell dedifferentiation in a human context. We discovered SOX9, HES1 and MYC as positive markers of human β cell dedifferentiation, demonstrating evidence for dedifferentiation process in human β cell
Mészáros, Gergő. "CaMK1D controls β-cell mass and glucose homeostasis". Thesis, Strasbourg, 2015. http://www.theses.fr/2015STRAJ035.
Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia resulting from defects in insulin secretion in combination with impaired insulin action. CaMK1D represents one potential candidate gene, the in vivo function remained elusive. In this work, I have found that CaMK1D plays a central role in blood glucose regulation. Pancreas-specific CaMK1D knockout mice display dramatically reduced fasting blood glucose levels leading to an overall improved glucose tolerance. CaMK1D knockout mice show markedly higher ad libitum and fasting insulin levels. Interestingly, pancreas-specific CaMK1D knockout mice display islet hyperplasia caused by beta-cell hypertrophy. Furthermore, conditional knockout mice are protected against high-fat feeding-induced hepatic steatosis. Overall, my work establishes an essential role of CaMK1D in pancreatic beta-cells and provides further understanding about its role in the development of T2DM
Goillot, Evelyne. "Expression de l'anomalie génétique déterminant les processus autoimmuns chez la souris NOD (non-obese diabetic) au niveau des cellules souches hématopoiétiques de foie foetal". Lyon 1, 1991. http://www.theses.fr/1991LYO1T065.
Philippe, Julien. "Étude des formes monogéniques de diabète de type 2 et d’obésité par le séquençage de nouvelle génération". Thesis, Lille 2, 2014. http://www.theses.fr/2014LIL2S049/document.
Diabetes and obesity have reached such proportions worldwide we are talking about pandemic. Both diseases are a major cause of mortality and multiple complications. Medical and financial issues are for both diseases a major public health problem. Two groups of factors contribute to these two diseases: environment, and genetics on which this thesis is based. This work focused on rare and monogenic forms which are extreme forms of type 2 diabetes and obesity.These forms are far from being fully understood. My project focused on the use of next generation sequencing (NGS) to identify more optimally, compared to conventional Sanger sequencing, mutations in already known genes among new patients in our cohort for diagnostic purposes. The second objective was to use NGS to discover new loci associated with new signaling pathways involved in the pathophysiology of diabetes and obesity.The first approach uses a liquid-phase hybridization technique and focuses on 34 genes associated with monogenic and/or polygenic obesity. The screening was carried out on 201 people in 13 families for which the cause of obesity is unknown. This approach led to the identification of a mutation in a known gene of obesity: PCSK1. This mutation is causal because it leads to a stop codon at the beginning of the protein and is present only in obese individuals. Additionally, functional studies have demonstrated partial inhibition of PC1/3 by the truncated protein and the possible impact on the processing and secretion of this enzyme. This study has been published published in the "International Journal of Obesity" newspaper.The second approach is based on a PCR amplification technique in lipid microdroplets developed by Raindance. The first test is to re-identify the causal mutations of diabetes and/or obesity in 40 patients. This approach has yielded satisfactory results because for a large majority of patients, the causative mutations have been identified again. Only one patient was unable to be reconfirmed because current bioinformatics tools are limited in the detection of complex indels. Of the 39 patients identified, 3 of them are potential carriers of several causative mutations. This technique could be considered in the clinical field because it allows a multigene approach by providing a rapid diagnosis, cheaper and with a quality similar to the gold standard Sanger sequencing. For us, the purpose of this technique is a fast and optimal clinical diagnosis in order to identify unsolved cases, which are candidates for exome sequencing. This second study was published in "Diabetes Care" journal.The third approach involves whole exome sequencing (WES) in 4 individuals where the whole family was previously tested negative for all known genes of diabetes. This approach led to the discovery of a thirteen MODY gene, KCNJ11, and confirms the broad phenotypic spectrum that goes from neonatal diabetes to MODY depending on the mutations. The major difficulty with this technique is filtering variants in order to get a single causal mutation (or possibly several on the same gene) to identify new MODY genes. The strategy we used combined both a bioinformatics filter for example with filters on family cosegregation and on SNP databases and a biological filter, with the use of a technique for high-throughput genotyping. This pioneering study in the use of NGS to identify new genes of MODY has been published in "PLoS ONE".In conclusion, this work took advantage of technological advances such as capture, targeted sequencing and NGS to elucidate and to improve the screening of monogenic forms of diabetes and obesity. This improved understanding of the molecular mechanisms may lead to the development of better treatments like personalized medicine. We hope to see direct improvements for patients in the near future, such as a more accurate, faster and more comprehensive molecular
Libri sul tema "Diabète non-insulinodépendant – Génétique":
Rabinow, Paul. French DNA: Trouble in Purgatory. University Of Chicago Press, 2002.
Rabinow, Paul. French DNA: Trouble in Purgatory. University Of Chicago Press, 1999.