EFFECTS OF CYCLOSPORINE-A AND VERAPAMIL ON MOUSE PANCREATIC-ISLETS

Treatment of NMRI mice with cyclosporin A (25 mg/kg body wt) for 11 da ys caused a marked fall in pancreas insulin content, although plasma g lucose and plasma insulin were unchanged. When islets from untreated m ice were exposed to cyclosporin A (2 mg/1) in vitro, no effect was see n in the first hour. After 24 h, cyclosporin A had significantly decre ased the islet content of insulin. Post-culture microperifusion showed that cyclosporin A for 24 or 72 h inhibited the insulin secretory res ponsiveness. Verapamil in vivo (0.4 mg/kg body wt per day) or in vitro (37.5 mug/1) did not modify these effects. Verapamil at 2 5 mg/l supp ressed the release of insulin but afforded no obvious protection again st cyclosporin A during culture. The beneficial action of verapamil on islets transplanted to the kidney may reflect renal events rather tha n a primary interaction of drugs in the islets.