Response to cyclosporine administration at onset of diabetes in BB rats.
The metabolic and immunological effects of cyclosporine A given at onset of spontaneous Type I diabetes in BB rats were examined, as an analogy to the current use of this agent in newly-diagnosed human diabetics. Diabetes-prone (BBdp) rats were monitored until appearance of hyperglycemia, at which time treatment with both cyclosporine (10 mg/kg/day) and insulin was immediately started. Cyclosporine induced no remission in any rats and did not affect their daily insulin requirements. After 9 weeks of cyclosporine treatment, islet morphology showed the typical "end-stage" picture in all rats, with essentially total beta cell loss. Pancreatic insulin contents were less than 1% of normal levels. During the 9 weeks of cyclosporine treatment, there was a decrease in numbers of peripheral blood Ia-positive lymphocytes, an increase in OX8+ lymphocytes (suppressor/cytotoxic and natural killer cells) but no change in the other subsets. There was a significant increase in plasma creatinine. We conclude that this dose of cyclosporine started at onset of diabetes in BB rats is unable to arrest and/or reverse the beta cell destructive process.
Yale
J F
JF
McGill Nutrition and Food Science Centre, McGill University, Montreal, QC, Canada.
Grose
M
M
Roy
R D
RD
Seemayer
T A
TA
Marliss
E B
EB
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003524:Cyclosporins / Q000097:blood / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D006029:Glycosuria; D007328:Insulin / Q000627:therapeutic use; D008214:Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB
D001786:Blood Glucose; D003524:Cyclosporins; D007328:Insulin