The effect of cyclosporin A on rat pancreatic B-cell: interaction with the calcium-antagonist diltiazem.
Cyclosporin A (CyA) was fed to male Wistar rats in a dose of 5, 10 or 50 mg/kg b.wt. for 7 days. In another experimental procedure 10 mg/kg b.wt. CyA was given for 7 days combined with Diltiazem (DIL) 6.25 mg/kg b.wt. once daily ip. Glucose stimulated insulin secretion from the isolated perfused pancreas was investigated in these animals. Total insulin secretion (ng/50 min) was not affected after feeding 5 mg/kg b.wt. CyA, but was significantly decreased with 10 and 50 mg/kg b.wt. CyA. The biphasic insulin secretion was reduced after 5 mg/kg b.wt. CyA during the initial peak (0-10 min) but not during the second peak (10-50 min), whereas after 10 and 50 mg/kg b.wt. CyA both peaks nearly reached base-line levels. DIL markedly increased the initial peak (0-10 min) after feeding CyA 10 mg/kg b.wt., whereas the second peak was not affected. Our results demonstrate a toxic effect of CyA on the pancreatic B-cell, which might be partly abolished by calcium-antagonists.
Stöckmann
F
F
Abteilung Gastroenterologie und Endokrinologie, Georg-August-Universität, Göttingen, FRG.
Fehmann
H C
HC
Haverich
R
R
Göke
B
B
Creutzfeldt
W
W
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D003524:Cyclosporins; D007328:Insulin; D004110:Diltiazem; D005947:Glucose