Bw. Tobin et al., INSULIN ACTION IN PREVIOUSLY DIABETIC RATS RECEIVING GRADED NUMBERS OF ISLETS OF LANGERHANS, Transplantation, 59(10), 1995, pp. 1464-1469
We characterized insulin sensitivity in islet transplanted rats receiv
ing from 500 to 3000 islets. Male Wistar Furth rats made previously di
abetic 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), Th
e acute insulin response to glucose (0.3 g/kg i.v.) was correlated wit
h 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 fas
ted, conscious animals during a hyperinsulinemic-euglycemic glucose cl
amp with insulin infused at 29 and 72 nmol/ kg/min. Despite a wide ran
ge of islet mass and insulin secretory capacity, there was no signific
ant difference in the glucose infusion rate between islet groups at ei
ther insulin level (P=0.8211, P=0.8021). There was also no difference
in the glucose infusion rate normalized to the prevailing insulin leve
l (P=0.1638, P=0.2302). Thus, our results demonstrate that the islet t
ransplanted rat is consistent with other animal studies and human stud
ies illustrating that a diminished insulin secretion does not necessar
ily precipitate insulin resistance.