NEW INSIGHTS INTO PANCREATIC BETA-CELL METABOLIC SIGNALING IN INSULIN-SECRETION

In recent years, it has become apparent that second messengers and fac tors 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 hypothese s in the field of beta-cell signaling. These include in particular tha t: 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: anap lerosis (the replenishment of the citric acid cycle with intermediates ) is essential for beta-cell activation: a shift from fatty acid oxida tion to esterification is an important event in beta-cell signaling: m alonyl-CoA and long chain acyl-CoA esters may act as metabolic couplin g factors: glycolytic oscillations underlie, in part, oscillations in electrical activity, cytosolic Ca2+ and insulin release. A metabolic m odel of fuel sensing that integrates the mode of action of all classes of nutrient secretagogues is proposed.