EVIDENCE THAT SUPPRESSION OF INSULIN-SECRETION BY INSULIN ITSELF IS NEURALLY-MEDIATED

We examined the mechanism by which an increase in blood insulin concentration inhibits insulin secretion by the pancreas. To this end, we determined plasma C-peptide concentrations during euglycemic-hyperinsulinemic (∼500 pmol/L) clamps in five patients with insulin-dependent diabetes mellitus (IDDM) after combined pancreas and kidney ( P K) transplantation, in five nondiabetic patients after kidney transplantation (K), and in six normal control subjects. Hyperinsulinemia decreased C-peptide concentrations in K patients (by 60%, P < .01) and controls (by 35%, P < .05), but not in P K patients (653 ± 115 v 702 ± 197 pmol/L before and after 4 hours of hyperinsulinemia, respectively). The main difference between K patients and controls and P K patients was that the pancreas in K patients and controls was innervated, whereas the transplanted pancreas of K P patients was denervated. The data therefore suggested that the inhibition of pancreatic insulin secretion by hyperinsulinemia was neurally mediated. © 1993.