Contact info

Dr Marc Prentki
CRCHUM · Technopôle Angus
2901, Rachel Street East – Room 401
Montreal, QC H1W 4A4

Tel: 1-514-890-8000, ext. 23642
Fax: 1-514-412-7648
E-mail: marc.prentki@umontreal.ca

Research keywords

Marc Prentki was trained in Biochemistry at the University of Geneva where he obtained a PhD degree. His thesis was in the field of the cytoskeleton, under the direction of Dr B. Jeanrenaud. He then joined the laboratory of Prof. Albert Renold in Geneva, where he worked as a post-doctoral fellow on intracellular Ca²⁺ homeostasis and insulin secretion. He next joined the laboratory of Dr F. Matschinsky at the University of Pennsylvania to work as a postdoctoral fellow on Ca²⁺ signaling, and was soon promoted to Research Assistant Professor in the Department of Biochemistry and Biophysics. He returned to Geneva to work as an Assistant Professor at the Institut de Biochimie Clinique. His research focus was on pancreatic ß-cell metabolic signaling and glucose regulation of gene expression. In 1994 he joined the Departments of Nutrition and Biochemistry at the University of Montreal where he is now full Professor.

In 2004, Dr Prentki, with the help of several investigators, founded the Montreal Diabetes Research Center that he currently directs. He was awarded the prize of the Federations of European Endocrine Societies in 1994 and a Canada Research Chair in Diabetes and Metabolism in 2006.

Click here for pdf CV

Dr Prentki showed that IP3 is a second messenger causing early mobilization of Ca²⁺ from the ER. He also observed using microfluorimetry that Ca²⁺ signals are oscillatory in the ß-cell in response to carbamylcholine and that the frequency of oscillations vary as a function of the agonist concentration. This suggested that frequency in addition to amplitude encodes cellular Ca²⁺ signaling.

The more recent research of Dr Prentki has increased our understanding of the mechanism of glucose regulated insulin secretion in health, obesity and diabetes. Notably he proposed together with Dr B. Corkey that malonyl-CoA acts as a metabolic signaling molecule in the ß-cell and that anaplerosis is implicated in glucose induced insulin secretion. More recent work from others has shown that malonyl-CoA also regulates insulin action, food intake and body weight at the level of the hypothalamus. In 1996, he introduced the concept of glucolipotoxicity that has important implication for the development of both Type 1 and 2 diabetes. His group also showed for the first time that GLP1 promotes ß-cell growth and protects the ß-cell from the glucolipotoxic insult. Dr Prentki has recently proposed that glycerolipid/fatty acid (GL/FA) cycling acts as a signaling and fuel detoxification machine producing signals for insulin secretion and action as well as cell growth. With respect to the field of metabolism and cancer, he provided possible links between obesity and cancer by showing that unsaturated fatty acids activate PI3-Kinase and the protooncogene PKB/Akt in breast cancer cells, and that their action on cell growth involves the fatty acid receptor GPR40 and possibly enhanced GL/FA cycling. Finally he co-directed with Drs Posner and Sladek a large-scale project on the genetics of type 2 diabetes. It led to the first successful whole genome scan for any disease and the identification of novel susceptibility loci.

Click here for PubMed listing

Current projects in the laboratory fall into two areas:

Metabolic signal transduction in the pancreatic ß-cell. We seek to identify the signals that mediate the link between fuel metabolism in the ß-cell and insulin release. In this respect we study the roles of pyruvate cycling processes, acyl-CoA compounds and GL/FA cycling.

Molecular basis of ß-cell compensation and failure in type 2 diabetes. Various animal models of obesity and type 2 diabetes are used to define the relative contributions of altered ß-cell growth and apoptosis, exhaustion and metabolic signal transduction. With respect to ß-cell adaptation to fuel surfeit and glucolipotoxicity the focus of the research is on the role of GL/FA cycling and ß-cell "dedifferentiation".

The laboratory addresses these investigations using a broad panoply of technologies including rodent KO models, RNA silencing, metabolomics/proteomics and transcriptomics, in vivo assessment of glucose/lipid metabolism and insulin signaling, as well as biochemical assays.