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Genomes and Genes | Vincent PoitoutSummaryCountry: Canada Publications
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Publications
Characterization of the human pancreatic islet proteome by two-dimensional LC/MS/MSThomas O Metz
Biological Science Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington, USA
J Proteome Res 5:3345-54. 2006..The resulting peptide reference library provides a resource for future higher throughput and quantitative studies of islet biology...
Glucolipotoxicity: fuel excess and beta-cell dysfunctionVincent Poitout
Montreal Diabetes Research Center, CR CHUM, Technopole Angus, 2901 Rachel Est, Montreal, Quebec, Canada H1W 4A4
Endocr Rev 29:351-66. 2008..Finally, we attempt to define the role of these phenomena in the natural history of beta-cell compensation, decompensation, and failure during the course of type 2 diabetes...
Glucolipotoxicity of the pancreatic beta cellVincent Poitout
Montreal Diabetes Research Center, CRCHUM, Department of Medicine, University of Montreal, Montreal, QC, Canada
Biochim Biophys Acta 1801:289-98. 2010..It is therefore likely that glucolipotoxicity contributes to beta-cell failure in type 2 diabetes as well as to the decline in beta-cell function observed after the onset of the disease...
Lipotoxicity impairs incretin signallingV Poitout
Montreal Diabetes Research Center, CRCHUM, Technopole Angus, 2901 Rachel Est, Montreal, QC, Canada
Diabetologia 56:231-3. 2013..These novel findings provide convincing support for the notion that restoring normal circulating lipid levels in type 2 diabetes might help improve the efficacy of incretin-based therapies...
Regulation of the insulin gene by glucose and fatty acidsVincent Poitout
Department of Medicine, University of Montreal, Montreal, QC, Canada
J Nutr 136:873-6. 2006..Glucotoxicity and lipotoxicity have common targets, which makes their combination particularly harmful to insulin gene expression and beta-cell function in type 2 diabetes...
Glucolipotoxicity of the pancreatic beta-cell: myth or reality?Vincent Poitout
Montreal Diabetes Research Center, Centre de recherche du Centre Hospitalier de l Universite de Montreal, Technopole Angus, 2901 Rachel Est, Montreal, QC, Canada, H1W 4A4
Biochem Soc Trans 36:901-4. 2008....
Phospholipid hydrolysis and insulin secretion: a step toward solving the Rubik's cubeVincent Poitout
Montreal Diabetes Research Center, CR-CHUM, Technopole Angus, 2901 Rachel Est, Montreal, Quebec, Canada
Am J Physiol Endocrinol Metab 294:E214-6. 2008
Lack of preservation of insulin gene expression by a glucagon-like peptide 1 agonist or a dipeptidyl peptidase 4 inhibitor in an in vivo model of glucolipotoxicityGhislaine Fontes
Montreal Diabetes Research Center, CRCHUM, University of Montreal, QC, Canada
Diabetes Res Clin Pract 87:322-8. 2010..Prolonged exposure of pancreatic beta-cells to elevated levels of glucose and fatty acids adversely affects insulin secretion and gene expression...
Deletion of GPR40 impairs glucose-induced insulin secretion in vivo in mice without affecting intracellular fuel metabolism in isletsThierry Alquier
Montreal Diabetes Research Center, Research Centre of the Montréal University Hospital, University of Montreal, Montreal, QC, Canada
Diabetes 58:2607-15. 2009..This study was aimed to ascertain whether GPR40 controls insulin secretion in vivo and modulates intracellular fuel metabolism in islets...
The fatty acid receptor GPR40 plays a role in insulin secretion in vivo after high-fat feedingMelkam Kebede
Montreal Diabetes Research Center, Centre de recherche du Centre Hospitalier de l Universite de Montreal, Montreal, Canada
Diabetes 57:2432-7. 2008..Glucose tolerance, insulin tolerance, and insulin secretion in response to glucose and Intralipid were assessed during the course of the diet period...
Pioglitazone acutely reduces insulin secretion and causes metabolic deceleration of the pancreatic beta-cell at submaximal glucose concentrationsJulien Lamontagne
Department of Nutrition and Biochemistry, Molecular Nutrition Unit and Montreal Diabetes Research Center, Universite de Montreal, Montreal, Quebec, Canada
Endocrinology 150:3465-74. 2009..We suggest that AMPK activation and the metabolic deceleration of the beta-cell caused by Pio contribute to its known effects to reduce hyperinsulinemia and preserve beta-cell function and act as an antidiabetic agent...
Cyclical and alternating infusions of glucose and intralipid in rats inhibit insulin gene expression and Pdx-1 binding in isletsDerek K Hagman
DVM, Montreal Diabetes Research Center, Centre de recherche du Centre Hospitalier de l Universite de Montreal, Technopole Angus, 2901 Rachel Est, Montreal, QC, H1W 4A4, Canada
Diabetes 57:424-31. 2008..Whether such a phenomenon also occurs in vivo is unknown. Our objective was therefore to ascertain whether chronic nutrient oversupply inhibits insulin gene expression in vivo...
Lipopolysaccharides impair insulin gene expression in isolated islets of Langerhans via Toll-Like Receptor-4 and NF-κB signallingJulie Amyot
Montreal Diabetes Research Center, Centre de recherche du Centre hospitalier de l Université de Montréal CRCHUM, Montreal, Quebec, Canada
PLoS ONE 7:e36200. 2012..In this study, we tested the hypothesis that LPS alters insulin gene expression via TLR4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in islets...
Binding of activating transcription factor 6 to the A5/Core of the rat insulin II gene promoter does not mediate its transcriptional repressionJulie Amyot
Montreal Diabetes Research Center, Centre de recherche du Centre hospitalier de l Université de Montréal CRCHUM, Technopole Angus, 2901 Rachel Est, Montreal, Quebec H1W 4A4, Canada
J Mol Endocrinol 47:273-83. 2011..Therefore, although ATF6 binds directly to the A5/Core of the rat insulin II gene promoter, this direct binding does not appear to contribute to its repressive activity...
Glucose activates free fatty acid receptor 1 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1Melkam Kebede
Montreal Diabetes Research Center, Centre de recherche du Centre Hospitalier de l Universite de Montreal, and Department of Medicine, University of Montreal, Montreal, QC, Canada H3T 1J4
Proc Natl Acad Sci U S A 109:2376-81. 2012..These observations reveal a unique mechanism by which glucose metabolism regulates the function of transcription factors in the nucleus to induce gene expression...
Involvement of Per-Arnt-Sim Kinase and extracellular-regulated kinases-1/2 in palmitate inhibition of insulin gene expression in pancreatic beta-cellsGhislaine Fontes
Montreal Diabetes Research Center, CRCHUM, University of Montreal, Quebec, Canada
Diabetes 58:2048-58. 2009..This study aimed to ascertain the role of extracellular-regulated kinases (ERKs)1/2, protein kinase B (PKB), and Per-Arnt-Sim kinase (PASK) in palmitate inhibition of insulin gene expression in pancreatic beta-cells...
Adipose triglyceride lipase is implicated in fuel- and non-fuel-stimulated insulin secretionMarie Line Peyot
Molecular Nutrition Unit and Montreal Diabetes Research Center, Centre de recherche du Centre Hospitalier de l Universite de Montreal, Montreal, Quebec H1W4A4, Canada
J Biol Chem 284:16848-59. 2009..The results demonstrate the importance of ATGL and intracellular lipid signaling for fuel- and non-fuel-induced insulin secretion...
GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivoMartin G Latour
Centre de recherche du Centre Hospitalier de l Universite de Montreal, Technopole Angus, 2901 Rachel Est, Montreal, QC, H1W 4A4 Canada
Diabetes 56:1087-94. 2007..We conclude that GPR40 contributes approximately half of the full acute insulin secretory response to fatty acids in mice but does not play a role in the mechanisms by which fatty acids chronically impair insulin secretion...
G protein-coupled receptors and insulin secretion: 119 and countingS R Murthy Madiraju
Montreal Diabetes Research Centre, University of Montreal, 2901 Rachel East, Montreal, Quebec, Canada
Endocrinology 148:2598-600. 2007
A role for the malonyl-CoA/long-chain acyl-CoA pathway of lipid signaling in the regulation of insulin secretion in response to both fuel and nonfuel stimuliRaphael Roduit
Molecular Nutrition Unit, Department of Nutrition, University of Montréal and the Centre Hospitalier de l Université de Montréal, Montreal, Quebec, Canada
Diabetes 53:1007-19. 2004..The data show the existence of important links between the metabolic coupling factor malonyl-CoA, the partitioning of fatty acids, and the stimulation of insulin secretion to both fuel and nonfuel stimuli...
Fatty Acid receptor gpr40 mediates neuromicrovascular degeneration induced by transarachidonic acids in rodentsJean Claude Honoré
Research Center CHU Ste Justine, Departments of Pediatrics, Ophthalmology, and Pharmacology, 3175, chemin Cote Ste Catherine, Montreal, Quebec, Canada H3T 1C5
Arterioscler Thromb Vasc Biol 33:954-61. 2013..CONCLUSIONS: GPR40 emerges as the first identified G protein-coupled receptor conveying actions of nonenzymatically generated nitro-oxidative products, specifically TAAs, and is involved in (neonatal) HI encephalopathy...
Palmitate inhibition of insulin gene expression is mediated at the transcriptional level via ceramide synthesisCynthia L Kelpe
Pacific Northwest Research Institute, Seattle, Washington 98122, USA
J Biol Chem 278:30015-21. 2003..We conclude that prolonged exposure to elevated levels of palmitate affects glucose-stimulated insulin gene expression via transcriptional mechanisms and ceramide synthesis...
The ins and outs of fatty acids on the pancreatic beta cellVincent Poitout
Pacific Northwest Research Institute and Department of Medicine, University of Washington, Seattle, WA, USA
Trends Endocrinol Metab 14:201-3. 2003
Beta-cell lipotoxicity: burning fat into heat?Vincent Poitout
Endocrinology 145:3563-5. 2004
Increasing triglyceride synthesis inhibits glucose-induced insulin secretion in isolated rat islets of langerhans: a study using adenoviral expression of diacylglycerol acyltransferaseCynthia L Kelpe
Pacific Northwest Research Institute, Seattle, Washington 98122, USA
Endocrinology 143:3326-32. 2002..We conclude that a selective increase in TG content impairs glucose-induced insulin secretion, a mechanism likely to mediate, at least in part, the deleterious effects of FA on pancreatic beta-cell function...
Elevated glucose attenuates human insulin gene promoter activity in INS-1 pancreatic beta-cells via reduced nuclear factor binding to the A5/core and Z elementMaria F Pino
Department of Physiology, Michigan State University, 3176 Biomedical and Physical Sciences Building, East Lansing, MI 48824, USA
Mol Endocrinol 19:1343-60. 2005....
The islet beta cell-enriched MafA activator is a key regulator of insulin gene transcriptionLi Zhao
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
J Biol Chem 280:11887-94. 2005..Collectively, these results suggest that MafA plays a key role in coordinating and controlling the level of insulin gene expression in islet beta cells...
Pancreatic islet response to hyperglycemia is dependent on peroxisome proliferator-activated receptor alpha (PPARalpha)Hélène Bihan
INSERM U 341, Hotel Dieu, Paris, France
FEBS Lett 579:2284-8. 2005..As such, islet PPARalpha could contribute to delay the progression of type 2 diabetes...
Palmitate inhibits insulin gene expression by altering PDX-1 nuclear localization and reducing MafA expression in isolated rat islets of LangerhansDerek K Hagman
Pacific Northwest Research Institute, Seattle, Washington 98122, USA
J Biol Chem 280:32413-8. 2005..These results demonstrate that prolonged exposure of islets to palmitate inhibits insulin gene transcription by impairing nuclear localization of PDX-1 and cellular expression of MafA...
Differential effects of hyperlipidemia on insulin secretion in islets of langerhans from hyperglycemic versus normoglycemic ratsIsabelle Briaud
Pacific Northwest Research Institute, Seattle, Washington 98122, USA
Diabetes 51:662-8. 2002..We conclude that hyperlipidemia induced by high-fat feeding affects insulin secretion in islets from hyperglycemic GK rats only, by a mechanism which may involve, at least in part, modulation of UCP-2 expression...
Insulin secretory deficiency and glucose intolerance in Rab3A null miceKazuro Yaekura
Pacific Northwest Research Institute and Departments of Pharmacology and Medicine, University of Washington, Seattle, Washington 98122, USA
J Biol Chem 278:9715-21. 2003..Also, this study indicates, for the first time, that the in vivo insulin secretory dysfunction found in type-2 diabetes can lie solely at the level of defective insulin exocytosis...
Effect of the two-layer (University of Wisconsin solution-perfluorochemical plus O2) method of pancreas preservation on human islet isolation, as assessed by the Edmonton Isolation ProtocolShinichi Matsumoto
Islet and Cell Processing Laboratory ICPL at Puget Sound Blood Center and Northwest Tissue Center, Seattle, WA, USA
Transplantation 74:1414-9. 2002..In this study, we hypothesized that the two-layer method (TLM) could extend the acceptable preservation period of pancreata before islet isolation and increase islet yields...
Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetesR Paul Robertson
Pacific Northwest Research Institute and the Departments of Medicine and Pharmacology, University of Washington, Seattle, Washington 98122, USA
Diabetes 53:S119-24. 2004....
Evidence against the involvement of oxidative stress in fatty acid inhibition of insulin secretionPatrick C Moore
Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122, USA
Diabetes 53:2610-6. 2004....
Minireview: Secondary beta-cell failure in type 2 diabetes--a convergence of glucotoxicity and lipotoxicityVincent Poitout
Pacific Northwest Research Institute, Seattle, Washington 98122, USA
Endocrinology 143:339-42. 2002..We propose that chronic hyperglycemia, independent of hyperlipidemia, is toxic for beta-cell function, whereas chronic hyperlipidemia is deleterious only in the context of concomitant hyperglycemia...
Research Grants
- Mechanisms of Fatty-Acid Inhibition of the Insulin GeneVincent Poitout; Fiscal Year: 2009..It will provide new therapeutic targets aimed at preserving insulin secretion in type 2 diabetes, a devastating disease that affects more than 18 million Americans. ..
- Mechanisms of Fatty-Acid Inhibition of the Insulin GeneVincent Poitout; Fiscal Year: 2007..It will provide new therapeutic targets aimed at preserving insulin secretion in type 2 diabetes, a devastating disease that affects more than 18 million Americans. ..
- Role of GPR40 in the regulation of insulin secretionVincent Poitout; Fiscal Year: 2005..As an alternative approach, we will knock down GPR40 expression in isolated adult mouse islets by RNA silencing using adenoviral technology. ..
- Neutral lipid dysregulation of the pancreatic beta-cellVincent Poitout; Fiscal Year: 2004..These experiments will provide important insights into the pathophysiology of beta-cell dysfunction of type 2 diabetes, and have clear implications for the treatment of this disease. ..
- Mechanisms of Fatty-Acid Inhibition of the Insulin GeneVincent Poitout; Fiscal Year: 2010..It will provide new therapeutic targets aimed at preserving insulin secretion in type 2 diabetes, a devastating disease that affects more than 18 million Americans. ..
