Abstract
Cyproheptadine (CPH) produced marked cytoplasmic vacuolization of pancreatic islet tissue after repeated oral administration of 22.5–90 mg/kg to the rat. No islet cell degeneration was observed in tissue from mice, rabbits, or hamsters after po administration. Intraperitoneal administration of CPH to rats caused only a slight degree of vacuolization. Examination of aldehyde-fuchsin-stained rat islet tissue after administration of CPH, 45 mg/kg for 2 wk, indicated a marked degranulation of beta cells. Electron microscopic examination of islet tissue from CPH-treated rats (45 mg/kg) showed vesiculation of the rough endoplasmic reticulum and loss of secretory granules in beta cells. These high doses of CPH produced a marked glucose intolerance in the rat as well as a diminished reponse of plasma insulin levels to glucagon stimulation.
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