Pancreatic beta cell changes induced by cyproheptadine in vitro

The effect of cyproheptadine on the structure and function of rat pancreatic beta cells was studied in vitro by culturing isolated islets in media containing the drug (0.5 mM). After 8 days in culture the ultrastructure of islet cells maintained in control media appeared well preserved, being similar to the previously reported for islets kept in long term organ culture. In contrast beta cells from islets incubated in media containing cyproheptadine appeared degranulated and the rough endoplasmic reticulum showed cisternal dilation and vacuole formation. These vacuoles were filled with an electron-dense granular material and their surface was usually studded with ribosomes. These lesions are identical with those produced by the administration of cyproheptadine to rats in vivo. In addition to these findings, increased numbers of lysosomes and myeloid bodies were observed in both alpha and beta cells. Compared with that of the controls, the 24-hour basal insulin secretion of islets cultured in the presence of cyproheptadine was significantly reduced from the 4th day of the study onwards. It is thus concluded that cyproheptadine has direct effects on the morphology and function of the rat pancreatic beta cell.