Pancreatic islet β-cells undergo structural changes in rats which are given daily 45 mg./kg. oral doses of cyproheptadine. The ultrastructural features of this lesion were studied after 1, 2, 4, 7, and 14 days of treatment. There was progressive degranulation of β-cells which was largely complete at two days, although a few granules were still evident at fourteen days. The rough endoplasmic reticulum underwent sequential changes of cisternal dilation, vesiculation, vesicle fusion, and vacuole formation. No normal appearing rough endoplasmic reticulum remained in β-cells of seven- and fourteen-day-treated rats. Ribosomes were lost from much of the surface of the vacuoles and vesicles which appeared to be derived from rough endoplasmic reticulum in these cells. Other cytoplasmic organelles of β-cells retained generally normal structure. Autophagy and necrosis were absent. Alteration in the glucose tolerance test was observed after two daily doses of cyproheptadine. Alpha and delta cells of islets and acinar cells appeared to be unaffected.

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