New insights into pancreatic β-cell metabolic signaling in insulin secretion

Abstract

Prentki M. New insights into pancreatic β-cell metabolic signaling in insulin secretion. Eur J Endocrinol 1996;134:272–86. ISSN 0804–4643 In recent years, it has become apparent that second messengers and factors other than ATP, metabolically sensitive K ATP+ channels and Ca 2+ 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 β-cell signaling. These include in particular that: a rise in cytosolic Ca 2+ is not sufficient to explain the kinetics and extent of secretion induced by glucose: variations in ADP, rather than ATP, regulate β-cell metabolism and the K ATP+ channel; anaplerosis (the replenishment of the citric acid cycle with intermediates) is essential for β-cell activation; a shift from fatty acid oxidation to esterification is an important event in β-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 Ca 2+ and insulin release. A metabolic model of fuel sensing that integrates the mode of action of all classes of nutrient secretagogues is proposed. Marc Prentki, Department of Nutrition, University of Montreal, CP6128, Succ, Centre-Ville, Montreal, PQ H3C3J7, Canada