Effects of cyclosporin A on insulin binding and action in isolated fat cells of rat.

To study the effect of cyclosporin A (CsA) on glucose metabolism in peripheral insulin target cells, we studied the intraperitoneal glucose tolerance test (i.p. GTT), insulin binding, glucose transport and lipogenesis in isolated adipocytes of CsA-treated male Wistar rats. The rats were treated for 7 days with an intramuscular injection of vehicle (control group), or 5 (group I) or 50 mg/kg body weight (group II) of CsA dissolved in ethanol. The results of i.p. GTT in group II showed markedly impaired glucose tolerance with significantly decreased basal and glucose-stimulated serum insulin levels. In isolated adipocytes of CsA-treated rats, the insulin bindings were decreased by 26% in group I and 32% in group II. The maximum insulin-stimulated glucose transports were decreased by 34% in group I and 41% in group II. The maximum insulin-stimulated lipogenesis was decreased by 33% in group I and 37% in group II. There was a right shift of the dose response curves for insulin of glucose transport and lipogenesis of both CsA-treated groups. In conclusion, these results suggest that CsA produces significant functional changes of pancreatic B cells and also induces insulin resistance in adipocytes due to combined receptor and postreceptor defects in insulin action.