Qualitative and semiquantitative calcium cytochemistry in B cells of mice treated with cyproheptadine and mannoheptulose

Abstract

The effect of cyproheptadine (CPH) and D-mannoheptulose (MH) on the function and the histo- (GBHA-method) and ultracytochemical (pyroantimonate method) calcium handling by pancreatic B cell were studied in mice. Intraperitoneal injection of CPH (45 mg/kg) or MH (1500 mg/kg) produced a hyperglycaemic syndrome, which was accompanied by decreased plasma insulin levels. CPH and MH also abolished glucose-induced insulin release. CPH led to a decrease of about 30 to 40% in the histochemical calcium content of islets as revealed by semi-quantitative microdensitometry, while MH did not change the calcium content of the islets. The ultracytochemical distribution pattern of calcium-rich precipitates were identical in CPH and MH treated B cells. The subcellular calcium deposits were predominantly located in the cytoplasmic matrix, but were rarely seen in granule halos and along the cell membranes. In contrast, glucose stimulation of the B cells resulted in an accumulation of the precipitates along the cell membranes and in the secretory granules. The results suggest that CPH and MH inhibit insulin release by either directly or indirectly interfering with the normal calcium handling by the B cell.