Hypertonic glucose impairs glucose-induced increases in cytosol Ca2+ concentration and insulin secretion by HIT-T 15...

To evaluate the mechanism of an impaired insulin secretion under diabetic state, we studied the influence of graded degrees of isotonic and hypertonic glucose on the rise in cytosol Ca2+ concentration ([Ca2+]i) and insulin secretion by HIT-T 15 cells. [Ca2+]i was monitored with Fura-2 and insulin secretion was measured with static culture. Both isotonic and hypertonic glucose induced a dose-dependent [Ca2+]i rise and insulin secretion. Although low degrees of isotonic and hypertonic glucose (5 and 15 mM) were equally effective to cause both increases in [Ca2+]i and insulin secretion, high degrees of isotonic glucose (30 and 60 mM) were clearly more effective than the same degrees of hypertonic glucose. The addition of 30 mM sucrose in isotonic 30 mM glucose also decreased the induced increases in [Ca2+]i and insulin secretion, and isotonic sucrose was ineffective in inducing either an increase in [Ca2+]i or insulin secretion. Removal of medium Ca2+ inhibited the 30 mM isotonic glucose-induced [Ca2+]i rise and insulin secretion. These data suggest that an impaired rise in [Ca2+]i, which was caused by blocking of Ca2+ influx due to hyperosmolarity, may be one mechanism by which glucose can not stimulate appropriate insulin secretion under diabetic state.