Signal transduction in the pancreatic β cell and regulation of insulin secretion. Glucose metabolism in the β cell triggers insulin secretion. The metabolic pathways involved in glucose-stimulated insulin secretion are still misunderstood. Our laboratory is working on the identification of the metabolic factors involved in coupling glucose metabolism and insulin secretion. We hypothesized that three metabolic cycles play a role in glucose-, fatty acid- and amino-acid-stimulated insulin secretion: the Krebs cycle, the pyruvate cycle and the glycerolipids/fatty acids cycle. With the help of a biochemical approach and molecular biology techniques such as the RNAi technology, adenovirus and KO mice, we are currently testing this hypothesis by overexpression or downregulation of key enzymes involved in intermediate metabolism regulation. We are also interested in the identification of genetic or nutritional defects (ex. excess of fatty acids) responsible for the aberrant insulin secretion in type 2 diabetes.

• Sladek,R., Rocheleau, G., Rung, J., Dina, C., Shen, L., Serre, D., Boutin, P., Vincent, D., Belisle, A., Hadjadj, S., Balkau, B., Heude, B., Charpentier, G., Hudson, TJ., Montpetit, A., Prentki, M., Posner, BI., Balding, DJ., Meyre, D., Polychronakos, C., and Froguel. P. A Genome-wide association study identifies novel susceptibility loci for Type 2 Diabetes mellitus. Nature 2007; 445:881-885.
• Peyot ML, Guay C, Latour MG, Lamontagne J, Lussier R, Pineda M, Ruderman NB, Haemmerle G, Zechner R, Joly E, Madiraju SR, Poitout V, Prentki M. Adipose Triglyceride Lipase Is Implicated in Fuel- and Non-fuel-stimulated Insulin Secretion. J Biol Chem 2009; 284:16848-59.
• Peyot ML, Pepin E, Lamontagne J, Latour MG, Zarrouki B, Lussier R, Pineda M, Jetton TL, Madiraju SR, Joly E. Prentki M. Beta-cell failure in diet-induced obese mice stratified according to body weight gain: secretory dysfunction and altered islet lipid metabolism without steatosis or reduced beta-cell mass. Diabetes 2010; 59:2178-87.
• Nolan, CJ, Damn, P. and Prentki M. Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet 2011; 378:169-81.
• Prentki M, Matschinsky FM, Madiraju SR. Metabolic signaling in fuel-induced insulin secretion. Cell Metab 2013; 18:162-185.
• Lamontagne J, Jalbert-Arsenault E, Pepin E, Peyot ML, Ruderman NB, Nolan CJ, Joly E, Madiraju SR, Poitout V, Prentki M. Pioglitazone acutely reduces energy metabolism and insulin secretion in rats. Diabetes 2013; 62:2122-2129.
• Zhao S, Mugabo Y, Iglesias J, Xie L, Delghingaro-Augusto V, Lussier R, Peyot M-L, Joly E, Davis MA, Brown JM, Abousalham A, Gaisano H, Madiraju SRM and Prentki M. ABHD6 accessible monoacylglycerol is a signal for glucose-stimulated insulin secretion. Cell Metab 2014;19:993-1007.
• Nolan, CJ, Ruderman, NB, Kahn, SE, Pedersen, O, Prentki M. Insulin resistance as a physiological defense against metabolic stress: implication for the management of subsets of type 2 diabetes. Diabetes 2015; 64: 673-86.
• Mugabo Y, Zhao S, Seifried A, Gezzar S, Al-Mass A, Zhang D, Lamontagne J, Attane C, Poursharifi P, Iglesias J, Joly E, Peyot ML, Gohla A, Madiraju SRM, and Prentki M. Identification of a mammalian glycerol-3-phosphate phosphatase: Role in metabolism and signaling in pancreatic β–cells and hepatocytes. Proc Natl Acad Sci USA 2016; 113:E430-E439.
• Zhao S, Mugabo Y, Ballentyne G, Attane C, Iglesias J, Poursharifi P, Zhang D, Nguyen TA, Erb H, Prentki R, Peyot ML, Joly E, Tobin S, Fulton S, Brown JM, Madiraju SRM, and Prentki M. α/β- Hydrolase domain-6 deletion induces adipose browning and prevents obesity and type-2 diabetes. Cell Reports 2016 In Press.