Impairment of stimulated insulin release from the isolated perfused rat pancreas by cyclosporine pretreatment.
Cyclosporine was fed to male Wistar rats in a dose of 5, 10, or 50 mg/kg b.wt. for 7 days, and the effect on insulin secretion from the isolated perfused pancreas was investigated. Dose-dependently plasma insulin and pancreatic insulin content decreased while whole-blood CsA levels increased. An increase in blood glucose was only observed after feeding 50 mg/kg b.wt. CsA resulting in whole-blood CsA levels of 7735 ng/ml. Glucose (20 mM)-stimulated total insulin secretion (ng/50 min) was not affected during feeding 5 mg/kg b.wt. CsA, but was significantly reduced after feeding 10 or 50 mg/kg b.wt. CsA. The biphasic insulin secretion was reduced after 5 mg/kg b.wt. during the initial peak (0-10 min) but not during the second peak (10-50 min), whereas after 10 or 50 mg/kg b.wt. CsA both peaks were markedly reduced. The arginine (20 mM) and the arginine (20 mM)-plus-glucose (20 mM) stimulated insulin secretion was less affected after feeding 10 mg/kg b.wt. CsA than after stimulation with glucose (20 mM) alone. The addition of CsA to the perfusate did not influence glucose-stimulated insulin release from normal rat pancreas. Our results demonstrate a toxic effect of CsA on the pancreatic beta cell that is dose dependent and possibly influences both insulin secretion and biosynthesis.
Stöckmann
F
F
Department of Medicine, University of Göttingen, FRG.
Fehmann
H C
HC
Göke
B
B
Siegel
E G
EG
Creutzfeldt
W
W
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects
D003524:Cyclosporins; D007328:Insulin; D001120:Arginine; D005947:Glucose