DEPENDENCE ON NADH PRODUCED DURING GLYCOLYSIS FOR BETA-CELL GLUCOSE SIGNALING

An increase in cytosolic ATP following glucose metabolism by pancreati c beta-cells is the key signal initiating insulin secretion by causing blockade of ATP-dependent K+ channels (K(APT)). This induces membrane depolarization, leading to an elevation in cytosolic Ca2+ ([Ca2+]i) a nd insulin secretion. In this report we identify the critical metaboli c step by which glucose initiates changes in beta-cell K(ATP) channel activity, membrane potential, and [Ca2+]i. The signal stems from the g lycolytic production of NADH during the oxidation of glyceraldehyde 3- phosphate, which is subsequently processed into ATP by mitochondria vi a the operation of discrete shuttle systems.