Cyclosporine-induced insulin release in rats is related to an increase in plasma lipid levels.
We studied the modifications of plasma lipid levels induced by cyclosporine (CsA), streptozocin (STZ) or both drugs in rats. Male Wistar rats (RT1y) were administered i.p. with CsA or STZ or both at the dosage of 15 mg/kg daily for 8 days and were sacrificed on day 9. Total lipid, triglyceride and total cholesterol plasma levels were measured. The plasma total lipid content was significantly increased in CsA-treated and in CsA + STZ-treated rats with respect to controls (662 +/- 29 and 632 +/- 32, respectively, vs 472 +/- 27 mg/dl). The triglyceride content was significantly higher in CsA-treated and in CsA + STZ-treated animals than in controls (137 +/- 8.7 and 188 +/- 14.1, respectively, vs 79 +/- 7.7 mg/dl). The total cholesterol level was not significantly different in CsA- and STZ-treated rats with respect to controls. CsA-treated and STZ-treated rats concomitantly revealed a significant impairment of glucose tolerance. In fact, 150 min after orogastric administration of 350 mg glucose, glycaemia was significantly more elevated in treated animals than in controls. We conclude that the increase in lipid levels induced by CsA treatment could be related to drug-induced damage to the pancreas islets, as shown by the early insulin release and fatty tissue degeneration.
Ferrero
M E
ME
Istituto di Patologia Generale, Università, Milan, Italy.
Marni
A
A
Parise
M
M
Salari
P C
PC
Corsi
M
M
Gaja
G
G
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D016572:Cyclosporine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D018149:Glucose Intolerance / Q000139:chemically induced; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014280:Triglycerides / Q000097:blood*
D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D013311:Streptozocin; D016572:Cyclosporine; D002784:Cholesterol