Beta-cell cytoplasmic Ca2+ balance as a determinant for glucose-stimulated insulin release.

The introduction of new techniques and the access to clonal lines of insulin-secreting cells have enabled re-evaluation of glucose effects on Ca2+ movements in pancreatic beta cells. It became evident that glucose, in addition to stimulating the entry of Ca2+, also promotes active sequestration of the ion in intracellular stores and its extrusion from the beta cells. The balance between these processes will determine the activity of Ca2+ in the cytoplasm and consequently the rate of insulin release. With the demonstration that glucose can not only increase but also lower cytoplasmic Ca2+, it follows that exposure to the sugar under certain conditions results in a paradoxical inhibition of insulin release. In diabetic patients this may be manifest as prompt reduction of circulating concentrations of insulin and C-peptide after an intravenous injection of glucose. The concept of the dual action of glucose might aid in explaining a number of poorly understood phenomena, such as the induction of rhythmic oscillations of the membrane potential of beta cells and the fact that their secretory response is improved by prolonged exposure to glucose and after priming with the sugar.