INSULIN SENSITIVITY AND NEGATIVE INSULIN FEEDBACK AFTER PANCREAS TRANSPLANTATION IN INSULIN-DEPENDENT DIABETIC-PATIENTS

The aims of this study were to determine the change in the rate of ins ulin-stimulated glucose disposal (insulin sensitivity) and the ability of insulin to inhibit its own secretion in four pancreas-kidney trans plant recipients with insulin-dependent diabetes mellitus. Insulin sen sitivity (glucose infusion rate, GIR) was measured by a euglycemic hyp erinsulinemic clamp technique before and 2, 6 and 12 months after tran splantation. The GIR values in the four recipients were normalized wit hin 2 months and remained normal for 12 months after transplantation, despite long-term steroid therapy for immunosuppression. Physiological hyperinsulinemia (50-70 mu U/ml) suppressed plasma C-peptide, but its nadirs were still higher than the basal levels in normal controls. Ta king into account evidence of a minimal increase in the concentration of circulating insulin that inhibits insulin secretion in healthy subj ects and evidence of increased insulin secretion in pancreas recipient s, the authors speculate that defective feedback inhibition of insulin secretion could contribute, at least in part, to the disproportionate basal hyperinsulinemia in patients with a denervated, transplanted pa ncreas in the absence of insulin resistance.