Metabolism-secretion coupling in glucose-stimulated insulin secretion.

Pancreatic β-cells in the islets of Langerhans secrete insulin in response to blood glucose levels. Precise control of the amount of insulin secreted is of critical importance for maintaining systemic carbohydrate homeostasis. It is now well established that glucose induced production of ATP from ADP and the KATP channel closure elevate cytosolic Ca2+, triggering insulin exocytosis in β-cells. However, for full activation of insulin secretion by glucose, other mechanisms besides Ca2+ elevation are needed. These mechanisms are the targets of current research and include intracellular metabolic pathways branching from glycolysis. They are metabolic pathways originating from the TCA cycle intermediates, the glycerolipid/free fatty acid cycle and the pentose phosphate pathway. Signaling effects of these pathways including degradation (removal) of protein SUMOylation, modulation of insulin vesicular energetics, and lipid modulation of exocytotic machinery may converge to fulfill insulin secretion, though the precise mechanisms have yet to be elucidated. This mini-review summarize recent advances in research on metabolic coupling mechanisms functioning in insulin secretion. © The Japan Diabetes Society 2022.