Evidence for normal in vitro Ca2+-stimulated insulin release in rats with non-insulin-dependent diabetes

Non-insulin-dependent diabetes (NIDD) was induced in adult rats following a neonatal injection of streptozotocin. Rats with NIDD exhibited moderate basal hyperglycemia (less than 2g/l) with defective glucose-induced insulin secretion and preserved or enhanced responsiveness to various non-glucose secretagogues. The possible sites of defects in the B cells of these diabetic rats are at present unknown. Extracellular Ca2+ at concentrations exceeding 10 mmol/l causes a dose-related stimulation of insulin release by the perfused normal rat pancreas. This technique provokes an increase of cytosolic Ca2+ accumulation in the B cell sufficient to trigger activation of the microtubular-microfilamentous effector system responsible for the exocytosis of insulin granules. It is therefore possible to compare functional efficiency of this process in the B cells of diabetic rats to that in the normal B cells. Results obtained in response to Ca2+ stimulation over the range 10-13.5 mmol/l provide evidence that the insulin release is stimulated in the pancreas of diabetic rats to the same extent as that in the controls, in both the kinetic and the quantitative aspect of the response. These data are compatible with the idea that in the B cells of rats with NIDD : 1) the effector system of insulin secretion is not grossly altered and 2) the lesion responsible for the loss of glucose-induced insulin secretion occurs before the effector system, involving either the mechanism by which glucose is metabolized as previously proposed by us, or another step yet to be identified.