Modulation of dihydropyridine-sensitive Ca²⁺ channels by glucose metabolism in mouse pancreatic β -cells

Abstract

GLUCOSE stimulates insulin secretion from the pancreatic β-cell by increasing the cytosolic calcium concentration¹. It is believed that this increment results mainly from Ca²⁺ influx through dihydropyridine-sensitive calcium channels because insulin secretion is abolished by dihydropyridine antagonists² and is potentiated by dihydropyridine agonists³. Glucose may influence Ca²⁺ influx through these channels in two ways: either by regulating the β-cell membrane potential or by biochemical modulation of the channel itself. The former mechanism is well established. Glucose metabolism, by closing ATP-sensitive K⁺ channels⁴, depolarizes the β-cell membrane and initiates Ca²⁺-dependent electrical activity, with higher glucose concentrations further increasing Ca²⁺ influx by raising the frequency of action potentials^5,6. We show here that glucose metabolism also increases calcium influx directly, by modulating the activity of dihydropyridine-sensitive Ca²⁺ channels.