The dual action of glucose on the cytosolic Ca2+ activity in pancreatic beta-cells. Demonstration of an inhibitory effect of glucose on insulin release in the mouse and man.

The cytosolic Ca2+ activity was measured with the fluorescent indicator quin-2 in pancreatic beta-cells obtained from obese-hyperglycemic mice. When present at a concentration of 20 mmol/l in a medium physiologically balanced in cations, glucose induced a rise of cytosolic Ca2+ after a delay of 1--3 min. At lower concentrations of extracellular Ca2+ this effect was not only prevented but the sugar promptly reduced the cytosolic Ca2+ activity. The dual effect of glucose on cytosolic Ca2+ had its counterpart in the release of insulin. Whereas 20 mmol/l of glucose stimulated the release of insulin from mouse islets previously stored in a Ca2+-deficient medium, the sugar was clearly inhibitory when present at a concentration of 6 mmol/l. Intravenous glucose tolerance tests revealed a temporary glucose depression of the serum concentrations of insulin and C-peptide in several patients with diabetes. In a mentally retarded girl with hyperinsulinemia associated with acanthosis nigricans the glucose suppression of circulating insulin was prolonged and sufficiently pronounced to suggest an almost complete inhibition of the secretory activity of the pancreatic B-cells.