Pancreatic transplantation in experimental non-insulin-dependent diabetic rats

The effect of pancreatic transplantation on noninsulin -dependent diabetes mellitus (NIDDM) had not been evaluated in animal models. We assessed its impact by the insulin-glucose clamp study in experimental diabetic rats. NIDDM was induced in Lewis female rats by streptozocin at the age of 5 days (n5-STZ). To determine its effect on insulin sensitivity, we measured the glucose turnover rate and performed euglycemic hyperinsulinemic clamp studies, evaluating hepatic glucose production (HGP) and glucose uptake. This assessment was conducted on 5 groups of 6 female Lewis rats: 2 groups n5-STZ tested at the age of 10 and 14 weeks, respectively; 2 normal age-matched groups; and a fifth group (n5-STZ) transplanted at 10 weeks of age and tested at 14 weeks. Heterotopic pancreaticoduodenal transplantation was performed, using an end-to-side anastomosis between the donor celiac artery and portal vein to the recipient infrarenal aorta and vena cava, respectively. Pancreatic drainage was achieved by an end-to-side duodenojejunostomy. At 10 weeks of age, diabetic n5-STZ rats showed decreased body weight, hyperglycemia, moderate insulinopenia, a significantly higher basal HGP as compared with normal controls (28.5 +/- 10 vs. 10.7 +/- 4 mg/kg/minute, P<0.05), and ineffective suppression of the HGP by the insulin infusion. Glycemia, body weight, and basal HGP were normalized in the transplanted group and were statistically similar to age-matched normal controls. HGP was totally suppressed by the insulin infusion. However, the blood insulin level remained significantly higher than in the normal groups (P<0.05). We conclude that n5-STZ is a reliable model of NIDDM and that pancreatic transplantation, without immunosuppressive drugs in this isogenic line, corrects all tested parameters of glucose homeostasis and improves insulin sensitivity.