Impaired glucose-induced calcium signal in pancreatic islets in chronic renal failure.

Abstract

Basal level of cytosolic calcium ([Ca2+]i) is elevated in islets of rats with chronic renal failure (CRF). The high [Ca2+]i level was implicated in the impaired insulin secretion of CRF, and its effect is due, in part, to a reduction in ATP content and impaired glucose metabolism by the islets. However, elevated [Ca2+]i may interfere with insulin secretion via another pathway. Exposure of the islets to glucose causes an acute rise in [Ca2+]i which generates events leading to insulin secretion. It is possible that a sustained rise in [Ca2+]i interferes with the magnitude of glucose-induced calcium signal and the ratio between this signal and basal [Ca2+]i. We examined this question in normal, CRF, normocalcemic CRF-PTX rats and in CRF rats treated with verapamil (CRF-V). Basal [Ca2+]i was higher (p less than 0.01) in CRF (130 +/- 7.0 nM) than in normal (82 +/- 5.5 nM), CRF-PTX (75 +/- 3.6 nM) and CRF-V rats (84 +/- 3.8 nM). Glucose-induced calcium signal (95 +/- 10.4 nM) and the ratio between this signal and basal [Ca2+]i (0.73 +/- 0.07) in CRF rats were lower (p less than 0.01) than in normal (153 +/- 14.4 nM; 1.90 +/- 0.24), CRF-PTX (130 +/- 16.7 nM; 1.75 +/- 0.25) and CRF-V (124 +/- 5.8 nM; 1.90 +/- 0.12) rats despite high PTH in the latter. The data indicate that a sustained rise in [Ca2+]i of islets interferes with the glucose-induced calcium signal which in turn plays a role in impaired insulin secretion.