Glyburide increases cytosolic-free calcium concentrations in normal rat pancreatic islet cells

Abstract

We have attempted to delineate the effect of glyburide on the regulation of cytosolic-free calcium concentrations, [Ca 2+]i, in normal rat pancreatic islet cells. In the presence of extracellular calcium (1 mmol/L), glyburide increased [Ca 2+]i from 70 nmol/L to 260 nmol/L in a dose-dependent manner. The maximal effect was seen at a concentration of 2 μmol/L with half-maximal stimulation observed at .25 μmol/L. The effect of glyburide (.25 μmol/L) was inhibited 90% by the calcium channel blocker, verapamil (30 μmol/L). At a maximally effective concentration of glyburide (2 μmol/L), the inhibitory effect of verapamil was only 17%. In the absence of extracellular calcium, glyburide increased [Ca 2+]i from 55 nmol/L to 107 nmol/L, indicating its ability to mobilize intracellular calcium stores. These results correlated well with the ability of glyburide (2 μmol/L) to stimulate insulin secretion both in the presence (from 38 ± 5 μmol/L/10 islets to 131 ± 28 μU/10 islets) and in the absence ( from 49 ± 4 μU 10 islets to 93 ± 7 μU 10 islets ) of extracellular Ca 2+. The present observations suggest that glyburide promotes calcium influx via voltage-dependent calcium channels and may mobilize intracellular calcium stores.