Comparison of portal and peripheral insulin delivery on carbohydrate metabolism in streptozotocin-diabetic rats.

Severely diabetic rats (150 mg streptozotocin/kg) were transplanted with fetal pancreatic islets: (a) under the kidney capsule to model peripheral insulin delivery, and (b) into the splenic pulp to model portal delivery. Long-term normoglycaemia, normal weight gain and normal peripheral insulin levels were achieved in both groups of transplanted animals. In both groups, 24-h fasted blood lactate, pyruvate and alanine were identical to those observed in sham-operated control animals. Blood glucose and plasma insulin responses to 300 mg oral glucose 8 weeks after transplantation were the same as in control animals. Hepatic glycogen concentration was, however, lower in fed rats with islets beneath the kidney capsule compared with control rats (p less than 0.01), suggesting inadequate hepatic insulinisation in the fed state with peripheral insulin delivery. Muscle glycogen was the same as in controls. Glucose turnover and glucose carbon recycling were not significantly different from results in normal control and splenic pulp islet-transplanted animals. The findings indicate that consistent normoglycaemia, normal glucose flux and normalisation of blood intermediary metabolites can be achieved in the rat with peripheral insulin delivery without associated hyperinsulinaemia.