Amelioration of hyperglycemia in streptozotocin-induced diabetic rats receiving a marginal mass of islet grafts by troglitazone, an oral antidiabetic agent

Troglitazone, a novel oral antidiabetic agent, was evaluated to determine whether it could have hypoglycemic effects in streptozotocin (STZ)-induced diabetic rats when a marginal mass of islets was transplanted and hyperglycemia persisted after transplantation. Lewis rats (RT1(1)) were used as both donors and recipients. Five hundred fresh islets were transplanted beneath the kidney capsule of STZ-induced diabetic recipients. Troglitazone was administered orally (0.34 mmol/kg/day) for 7 days before and for 60 days after islet transplantation. Neither troglitazone treatment without islet transplantation (n = 8) nor islet transplantation alone (n = 7) could produce normoglycemia (<11 mmol/L) in diabetic recipients by 60 days after transplantation. In marked contrast, seven of 10 rats receiving islet grafts and treated with troglitazone became normoglycemic at 26.9 +/- 16.4 days (mean +/- SD; n = 7) after transplantation. Removal of the kidney bearing the grafts promptly resulted in the normoglycemic recipients (n = 4) becoming diabetic again. Light and electron microscopically, the intact islets with well-granulated beta cells could be observed in the transplant site of the normoglycemic recipients. These findings clearly demonstrate that the hyperglycemia in STZ-induced diabetic rats receiving an insufficient number of islet grafts to reverse diabetes was ameliorated by troglitazone treatment.