Glucose inhibits insulin release when not promoting the entry of calcium into the β-cells

Abstract

The basal Ca 2+ permeability of islets from ob ob -mice was raised by culture in a Ca 2+-deficient medium. The resulting secretory activity upon transfer to a higher Ca 2+ concentration was significantly inhibited by 6 mM glucose although higher concentrations of the sugar further stimulated insulin release. In the presence of theophylline, the inhibitory effect of 6 mM glucose was altered into a stimulatory one. After blocking the voltage-dependent channels for Ca 2+ with D-600, 20 mM glucose did not enhance but significantly inhibited insulin release. The demonstration of a paradoxical glucose inhibition of insulin release is in accordance with recent reports that the sugar not only increases but also can lower the cytoplasmic Ca 2+ activity in the pancreatic β-cells.