The effect of combination therapy with cyclosporine A and hydrocortisone on glucose metabolism in diabetic rats following pancreatic islet transplantation.
Glucose tolerance, insulin secretion and in vitro insulin action were examined in streptozotocin-induced diabetic rats following pancreatic islet allotransplantation treated with combination of oral cyclosporine A (10 mg/kg) and hydrocortisone (1.5 mg/kg) intramuscularly. 1400 pure islets from multiple donors were implanted either into the portal vein (n = 10) or under the renal capsule (n = 11). Ten sham-operated non-diabetic animals receiving the same immunosuppressive therapy, 8 healthy animals without any treatment and 10 diabetic animals without immunosuppression following islet transplantation were used as controls. In all transplanted animals blood glucose was normalized by day 3 after transplantation with lower levels in those transplanted intraportally (p < 0.05). Non-immunosuppressed animals rejected the graft after 6.5 +/- 1.2 days after transplantation, immunosuppressed animals in both groups remained normoglycaemic till the end of the experiment on day 28. Oral glucose tolerance tests and insulin levels on days 10 and 28 improved dramatically. No differences in glucose and insulin levels between intraportal and subcapsular groups were found. Post-load glucose levels in immunosuppressed non-transplanted animals were higher on day 28 than before treatment and were also higher than in the healthy non-treated group (p < 0.05). In vitro insulin action determined by the incorporation of labelled glucose into adipose tissue was impaired only in animals in which islets were transplanted into the liver (p < 0.05 vs other groups). In conclusion, therapy with cyclosporine A and hydrocortisone prevents allogeneic islet rejection in rats during a short-term experiment. Although glucose tolerance is not completely normalized following transplantation, slight impairment is also demonstrable in healthy animals on the same drug therapy.
Saudek
F
F
Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Kazdová
L
L
Nozicková
M
M
Vrána
A
A
Cíhalová
E
E
Ruzbarský
V
V
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001786:Blood Glucose; D002250:Carbon Radioisotopes; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000601:surgery; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005215:Fasting; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006854:Hydrocortisone / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000166:cytology; D050356:Lipid Metabolism; D008099:Liver / Q000098:blood supply / Q000166:cytology; D011169:Portal Vein / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007166:Immunosuppressive Agents; D007328:Insulin; D016572:Cyclosporine; D003404:Creatinine; D005947:Glucose; D006854:Hydrocortisone