SEX STEROIDS DO NOT PREVENT AMYLIN-INDUCED APOPTOSIS IN HUMAN-CELLS

Formation of amylin-containing islet amyloid deposits may contribute t o the progressive deterioration of beta cell function in non-insulin-d ependent diabetes mellitus. As diabetes mellitus occurs in male, but r arely in female transgenic mice expressing human amylin in their pancr eatic beta cells, it is of interest to study the influence of estradio l (E-2) and testosterone (T) on amylin-induced cytotoxicity in human c ells. The insulinoma cell line CM, thyroid epithelial cells (TEC) in p rimary culture, and nontransformed fibroblast lines were used. The occ urrence of apoptotic cell death was assessed by nuclear labeling with propidium iodide, Amylin was cytotoxic on all cell types tested, but h ad the most pronounced effect on TEC and the weakest on the CM cell li ne. Although both E-2 and T decreased the proportion of apoptotic cell s in cultures kept in the absence of amylin, neither of the two hormon es was able to counteract amylin-induced cytotoxicity. beta cell death and hyperglycemia can thus presumably not be prevented by the neutral ization of amylin effects by sex steroids. (C) 1998 Academic Press.