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.
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D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D050356:Lipid Metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins; D007328:Insulin; D005947:Glucose