Effects of sulfonylureas on histochemical and ultracytochemical calcium distribution in B-cells of mice

Abstract

The study examines the effects of sulfonylurea compounds on the histo- and ultracytochemical calcium distribution within the B-cells of mice using the glyoxal-bis-(2-hydroxyanil) (GBHA) and the pyroantimonate method combined with X-ray microanalysis. Treatment with tolbutamide (200 mg/kg), glibenclamide (2 mg/kg) and glisoxepide (2 mg/kg), causing moderate hypoglycemia and B-cell degranulation, was associated with an unchanged (30, 90 min) or slightly increased (180, 360 min, 4, 42d) GGHA staining intensity of the islet cells compared with controls. Ultra-cytochemically sulfonylureas provoked, compared with controls, a redistribution of calcium-rich, electron dense pyroantimonate precipitates (EDPP). Precipitation predominantly occurred along the inner surface of the plasma membranes and within the granule halos. In contrast, the cytoplasmic matrix, the Golgi complexes and the rough endoplasmic reticulum contained only few fine precipitates. The sulfonylureas investigated exerted identical effects on the histo- and ultracytochemical calcium distribution in B-cells. The results indicate that sulfonylurea-induced insulin secretion is associated with an accumulation and redistribution of calcium within the B-cells. This supports the hypothesis that an altered calcium handling by the B-cell mainly accounts for the insulinotropic effect of sulfonylureas.