The ability of insulin to inhibit its own secretion was examined in 15 normal subjects given an intravenous infusion of insulin in a dose of 0.25, 0.50, 1.0, 5.0 or 10.0 mU/kg/min for two hours. Arterial plasma insulin concentration achieved during the infusion segregated into three levels of hyperinsulinaemia: 35±1 (mean ±SEM), 87±15 and 828±210 μU/ml. Plasma glucose concentration was kept constant at the basal level by a variable glucose infusion. Fasting C-peptide (0.29±0.02 pmol/ml) fell significantly in all subjects during hyperinsulinaemia and reached a concentration of 0.19±0.03 pmol/ml at 60 min and 0.14±0.03 at 120 min after the start of the insulin infusion. The C-peptide response was not related to the infusion dose nor to the steady state plasma insulin concentration. It is concluded that (a) basal insulin secretion as evaluated from C-peptide measurements is inhibited by small (24±3 μU/ml) physiological elevations in plasma insulin concentration independent of changes in plasma glucose, and (b) supraphysiological or even pharmacological elevations in plasma insulin do not result in a further decrease in endogenous insulin secretion above that achieved with mild hyperinsulinaemia.
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