Significance of the calcium content of mouse beta cells in the preservation of glucose-induced insulin release during culture.

Pancreatic islets containing more than 90% beta cells from obese-hyperglycaemic (ob/ob) mice were cultured for 3 days in different concentrations of Ca2+ and glucose to evaluate the importance of intracellular Ca2+ sequestration in glucose-induced insulin release. The islet contents of calcium (total and exchangeable) and immunoreactive insulin were compared with the insulin secretory response to glucose after culture. The turnover of Ca2+ increased with increasing concentrations of glucose and Ca2+. Islets cultured in the presence of 5.5 mmol glucose/l contained more calcium and insulin than those cultured with 1 or 20 mmol glucose/l. During culture in 20 mmol glucose/l, a lowering of the Ca2+ concentration of the medium from 0.42 to 0.025 mmol/l resulted in a paradoxical increase in intracellular calcium, with improvement of the subsequent secretory response to the sugar. When the islets had been exposed to the calcium channel blocker D-600 during culture in a Ca2+-deficient medium, substantial insulin release was noted from islets containing relatively small amounts of calcium. The results suggest that the well-established role of glucose in maintaining insulin release is associated with an ability of the sugar to stimulate the retention of calcium in beta cells.