New insights into pancreatic beta-cell metabolic signaling in insulin secretion.
In recent years, it has become apparent that second messengers and factors other than ATP. metabolically sensitive K+ATP channels and Ca2+ play essential roles in nutrient-induced insulin release. This paper reviews the evidence in support of several new concepts and hypotheses in the field of beta-cell signaling. These include in particular that: a rise in cytosolic Ca2+ is not sufficient to explain the kinetics and extent of secretion induced by glucose; variations in ADP, rather than ATP, regulate beta-cell metabolism and the K+ATP channel; anaplerosis (the replenishment of the citric acid cycle with intermediates) is essential for beta-cell activation: a shift from fatty acid oxidation to esterification is an important event in beta-cell signaling: malonyl-CoA and long chain acyl-CoA esters may act as metabolic coupling factors; glycolytic oscillations underlie, in part, oscillations in electrical activity, cytosolic Ca2+ and insulin release. A metabolic model of fuel sensing that integrates the mode of action of all classes of nutrient secretagogues is proposed.
Prentki
M
M
Department of Nutrition, University of Montreal, Canada.
D000818:Animals; D004704:Endocrinology / Q000639:trends*; D006019:Glycolysis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000502:physiology*; D008055:Lipids / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D008954:Models, Biological; D009747:Nutritional Physiological Phenomena; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D015398:Signal Transduction
D007328:Insulin; D008055:Lipids; D011773:Pyruvates; D019289:Pyruvic Acid