Single pancreatic β-cells from normal rats exhibit an initial decrease and subsequent increase in cytosolic free Ca 2+ in response to glucose

Abstract

Since it was reported that glucose stimulation initially lowers as well as subsequently raises the cytosolic free calcium concentration ([Ca 2+] i) in pancreatic islet cells from hyperglycemic ob ob mice, it has been argued whether the lowering of [Ca 2+] i is physiological or artifactual. In the present study, [Ca 2+] i in single pancreatic β-cells from normal rats was measured by Fura-2 microfluorometry. Following elevation of the glucose concentration from 2.8 mM (basal) to 16.7 mM, a bimodal change in [Ca[ 2+] i, an initial decrease and subsequent increase, was demonstrated. When the basal glucose concentration was raised to 5.6 mM, the stimulation with 16.7 mM glucose also induced the decrease in [Ca 2+] i in the majority of the cells, though the amplitude of the decrease was reduced. An elevation of the glucose concentration from 2.8 to 5.6 mM induced the decrease in [Ca 2+] i but not usually the increase in [Ca 2+] i. Removal of extracellular Ca 2+ eliminated the increase in [Ca 2+] i without affecting the decrease in [Ca 2+] i. Thus, the decrease and increase in [Ca 2+] i were clearly dissociated under certain conditions. In contrast, mannoheptulose (an inhibitor of glucose metabolism) inhibited both the decrease and increase in [Ca 2+] i. These results demonstrate that the glucose-induced bimodal change in [Ca 2+] i is a physiological response of islet β-cells, and that the decrease and increase in [Ca 2+] i are generated by mutually-independent mechanisms which are operated through glucose metabolism by islet β-cells.