Selective impairment of the cytoplasmic Ca2+ response to glucose in pancreatic beta cells of streptozocin-induced non-insulin-dependent diabetic rats.

Pancreatic islets from the streptozocin-induced non-insulin-dependent diabetes mellitus (NIDDM) rat model showed a diminished insulin response to 16.7 mmol/L glucose, but the insulin response to arginine remained intact. To evaluate the importance of intracellular calcium concentration ([Ca2+]i) in the diminished insulin response to glucose, the [Ca2+]i of pancreatic beta cells was investigated using fura-2. Glucose produced heterogeneous responses of [Ca2+]i, which were in beta-cell clusters of both the control and NIDDM groups. Many cells showed initial slight decreases of [Ca2+]i, which were followed by gradual and large increments of [Ca2+]i after glucose stimulation of beta cells in the control group. On the other hand, the increase of [Ca2+]i in response to glucose was markedly diminished in beta cells of the NIDDM group compared with controls. The average lag time to [Ca2+]i elevation of beta cells in the NIDDM group was significantly longer than that of the control group. Arginine produced marked increases of [Ca2+]i, in contrast to the effect of glucose stimulation in the NIDDM group. These results suggest that the diminished and delayed [Ca2+]i increases in beta cells of NIDDM rats in response to glucose stimulation are responsible for the selectively impaired insulin response to glucose in the rat model of NIDDM.