Alteration of pancreatic B-cells in Wistar rats treated with non-diabetogenic doses of cyclosporin A.
We have investigated the effect of non-immunosuppressive cyclosporin A (CS-A) doses on glucose tolerance, pancreatic insulin content, insulin content of isolated islets and insulin secretion in vitro in response to glucose. Within 12 weeks animals treated permanently with a dose of 2.5 mg CS-A/kg b.wt. developed glucose intolerance (but not hyperglycaemia) accompanied by a decrease of pancreatic insulin content due to a decrease of islet insulin content, whereas the relative B-cell volume density was not changed. Isolated islets obtained from rats treated for 4 weeks had a diminished sensitivity for glucose, whereas islets obtained from animals treated for greater than 4 weeks showed a diminished half-maximum and maximum secretion rate. Rats treated for 12 weeks with 1.25 mg CS-A/kg b.wt. developed an impaired glucose tolerance after 8 weeks accompanied by a diminished pancreatic insulin content. Despite continued treatment the pancreatic insulin content was able to increase and the glucose tolerance to normalize, indicating an adaptation of pancreatic B-cells to CS-A. The results support the theory that a potential toxic effect of cyclosporin A can be diagnosed by functional tests (e.g. insulin secretion in response to a stepwise increase of glucose) before the irreversible (e.g. morphological) alterations occur.
Hahn
H J
HJ
Institute of Diabetes G. Katsch, Karlsburg, Germany.
Laube
R
R
Lucke
S
S
Besch
W
W
D000818:Animals; D001663:Bilirubin / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007273:Injections, Intramuscular; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D016572:Cyclosporine; D003404:Creatinine; D001663:Bilirubin