title: Signal transduction mechanisms in nutrient-induced insulin secretion.
abstract: The knowledge of the mechanism whereby glucose and other fuel stimuli promote the release of insulin by the pancreatic beta cell remains fragmentary. The closure of metabolically sensitive K+ channels and a rise in cytosolic free Ca2+ are key features of beta-cell metabolic signal transduction. However, these two signalling events do not account for the dose dependence of glucose-induced insulin secretion. In fact, recent evidence indicates that there are KATP channel and Ca2+ independent pathway(s) of beta-cell activation which remain to be defined. In this review, we have limited our attention to the recent developments in our understanding of the mode of action of nutrient secretagogues. A particular emphasis is placed in summarising the evidence in support of two new concepts: 1) oscillations in the glycolytic pathway and beta-cell metabolism contribute to the oscillatory nature of beta-cell ionic events and insulin secretion; 2) malonyl-CoA and long chain acyl-CoA esters may act as metabolic coupling factors in beta-cell signalling. Finally, we propose that the altered expression of genes encoding enzymes in the pathway of malonyl-CoA formation and fatty acid oxidation contributes to the beta-cell insensitivity to glucose in some patients with non-insulin-dependent diabetes mellitus.
authors.affiliation: Department of Nutrition and Centre de Recherche L.-C. Simard, Institut du Cancer de Montreal, University of Montreal, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Prentki
authors.forename: K
authors.initials: K
authors.lastname: Tornheim
authors.forename: B E
authors.initials: BE
authors.lastname: Corkey
mesh_terms: D000818:Animals; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007328:Insulin; D008316:Malonyl Coenzyme A