Immediate but not long-term administration of nicardipine inhibits tolbutamide-induced insulin secretion from rat pancreatic beta cells.

OBJECTIVES

Calcium channel blockers alter glucose homeostasis, but sufficient data regarding this effect in healthy animals have not been provided. We test the effect of nicardipine on beta cell function in healthy rats.

METHODS

Islets from Sprague-Dawley rats were coincubated with nicardipine, tolbutamide, or their combination for 1 hour. Insulin secretion was measured by radioimmunoassay. The rats were given nicardipine, tolbutamide, or their combination by intravenous injection. Intravenous glucose tolerance tests were performed after the first drug administration and 4 weeks later. Pancreata were excised for assessment of insulin content and immunohistochemical staining in the end.

RESULTS

Nicardipine markedly inhibited not only the insulin secretion by islets per se but also that enhanced by tolbutamide in vitro. Blood glucose was reduced by tolbutamide in vivo but elevated by nicardipine abruptly in parallel with retarded insulin secretion. Long-term administration of nicardipine altered neither fasting blood glucose level nor fasting serum insulin level, whereas pancreatic insulin content was unmodified despite that nicardipine caused shrunken islets with weak immunoreactivity of beta cells by immunohistochemistry.

CONCLUSIONS

In healthy rats, immediate administration of nicardipine inhibits insulin secretion of beta cells both in vitro and in vivo but does not exert a deleterious effect in vivo after long-term treatment.