Glucose metabolism by rat pancreatic beta-cells produces dual change in cytosolic Ca2+.

It was reported that glucose stimulation initially lowers as well as subsequently raises the cytosolic free calcium concentration ([Ca2+]i) in pancreatic islet cells from hyperglycemic ob/ob mice. In the present study, [Ca2+]i in single pancreatic beta-cells from normal rats was measured by fura-2 microfluorometry. Following elevation of the glucose concentration to 16.7 mM from either 2.8 mM (basal) or 5.6 mM, an initial decrease and subsequent increase in [Ca2+]i were demonstrated. An elevation of the glucose concentration from 2.8 to 5.6 mM induced the decrease in [Ca2+]i but not usually the increase. Removal of extracellular Ca2+ eliminated the increase in [Ca2+]i without affecting the decrease. Mannoheptulose and KCN, inhibitors of glucose metabolism and TCA cycle, eliminated both the decrease and increase in [Ca2+]i. These results demonstrate that the glucose-induced bimodal change in [Ca2+]i is a physiological response of islet beta-cells, and that the decrease and increase in [Ca2+]i are generated by mutually-independent mechanisms which are operated through glucose metabolism by islet beta-cells.