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 (approximately 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.