Sensitivity of insulin secretion to feedback inhibition by hyperinsulinaemia

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Abstract
The ability of insulin to inhibit its own secretion was examined in 15 normal subjects given an i.v. infusion of insulin in a dose of 0.25, 0.50, 1.0, 5.0 or 10.0 mU/kg per min for 2 h. Arterial plasma insulin concentration achieved during the infusion segregated into 3 levels of hyperinsulinemia: 35 .+-. 1 (mean .+-. standard error of the mean), 87 .+-. 15 and 828 .+-. 210 .mu.U/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 hyperinsulinemia 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. Basal insulin secretion as evaluated from C-peptide measurements is inhibited by small (24 .+-. 3 .mu.U/ml) physiological elevations in plasma insulin concentration independent of changes in plasma glucose, and supraphysiological or even pharmacological elevations in plasma insulin do not result in a further decrease in endogenous insulin secretion above that achieved with mild hyperinsulinemia.

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