Amelioration of streptozotocin-induced diabetes in rats: Effect of islet isografts on plasma lipids and other metabolic abnormalities

Administration of streptozotocin in rats results in many metabolic abnormalities, including hyperlipidemia. Plasma triglycerides, cholesterol, insulin, and glucose levels were compared in normal rats, in rats with streptozotocin-induced diabetes, and in streptozotocin-injected rats ameliorated of diabetes 1 mo later by transplantation of adult or neonatal islets to the liver or the lung. Mean plasma glucose levels were 98 ± 4 mg/dl in normal rats, 504 ± 36 mg/dl in untreated diabetic rats, and 139 ± 18, 146 ± 9, and 117 ± 19 mg/dl in recipients of intraportal adult islets, intraportal neonatal islets, and i.v. neonatal islets, respectively; the glucose levels in the recipients of intraportal islets were significantly higher than in normal rats. Mean plasma insulin levels were 23 ± 4 μU/ml in normal rats, 12 ± 5 μU/ml in diabetic rats, and 46 ± 14, 84 ± 25, and 30 ± 5 μU/ml in recipients of intraportal adult islets, intraportal neonatal islets, and i.v. neonatal islets, respectively; the insulin levels in the recipients of intraportal islets were also significantly higher than those in normal rats. Mean plasma triglyceride levels were 35 ± 3 mg/dl in normal rats, 280 ± 72 mg/dl in diabetic rats, and 49 ± 9, 58 ± 8, and 70 ± 4 mg/dl in recipients of intraportal adult islets, intraportal neonatal islets, and i.v. neonatal islets, respectively; the levels in recipients of neonatal islets were significantly higher than those in normal rats. Mean plasma cholesterol levels were 122 ± 10 mg/dl in normal rats, 88 ± 13 mg/dl in diabetic rats, and 105 ± 10, 166 ± 19, and 114 ± 18 mg/dl in recipients of intraportal adult islets, intraportal neonatal islets, and i.v. neonatal islets, respectively; the levels were significantly higher than normal only for the group receiving neonatal islet tissue via the portal vein. Islet transplantation ameliorated diabetes, but mild hyperglycemia persisted even though plasma insulin levels were elevated above normal in recipients of intraportal islets. In addition, plasma triglyceride levels remained slightly elevated after transplantation of neonatal islets, and cholesterol levels were elevated in the group with the highest insulin levels. Possible mechanisms to explain the abnormalities after islet transplantation are discussed. The results indicate the difficulty in restoring completely normal metabolism by ectopic islet transplantation in diabetic recipients.