INSULIN ACTION IN PREVIOUSLY DIABETIC RATS RECEIVING GRADED NUMBERS OF ISLETS OF LANGERHANS

We characterized insulin sensitivity in islet transplanted rats receiving from 500 to 3000 islets. Male Wistar Furth rats made previously diabetic with streptozotocin (55 mg/kg) were infused intraportally with islets of Langerhans (500 islets: n=8; 1000: n=6; 2000: n=6; 3000: n=5) from syngeneic donors and compared with sham-operated controls (n=7). At four weeks after islet transplantation, fasting blood glucose was not significantly different between groups (500: 5.1+/-0.3; 1000: 4.8+/-0.3; 2000: 5.1+/-0.3; 3000: 4.6+/-0.1; control: 4.7+/-0.2 mM; P = 0.6146), and fasting plasma insulin was also not different (P=0.28), The acute insulin response to glucose (0.3 g/kg i.v.) was correlated with islet equivalent mass (r=0.63, P=0.004; transplant rats only); islet transplant animals presented a range of acute insulin secretion from 3 to 90% of control values. Insulin action was measured in vivo in fasted, conscious animals during a hyperinsulinemic-euglycemic glucose clamp with insulin infused at 29 and 72 nmol/ kg/min. Despite a wide range of islet mass and insulin secretory capacity, there was no significant difference in the glucose infusion rate between islet groups at either insulin level (P=0.8211, P=0.8021). There was also no difference in the glucose infusion rate normalized to the prevailing insulin level (P=0.1638, P=0.2302). Thus, our results demonstrate that the islet transplanted rat is consistent with other animal studies and human studies illustrating that a diminished insulin secretion does not necessarily precipitate insulin resistance.