Insulin Secretion and Clearance: Comparison After Oral and Intravenous Glucose

Abstract

Insulin secretion and clearance in response to the administration of oral and intravenous glucose was investigated in nine normal men. C-peptide metabolic kinetics were calculated by analysis of individual C-peptide decay curves after the bolus injection of biosynthetic human C-peptide. Glucose was administered to the subjects on three occasions: as a 75-g oral dose, a 75-g i.v. infusion, and an intravenous glucose infusion at a variable rate adjusted to mimic the peripheral glucose levels obtained after the oral glucose load (matching experiment). Glucose, insulin, and C-peptide concentrations were measured for the subsequent 5 h. The glucose level after the oral glucose load (115.9 ± 2.6 mg/dl, mean ± SE) closely approximated that after the matching experiment (120.5 ± 2.5 mg/dl) but was significantly lower than after 75 g i.v. glucose (127.7 ± 3.4 mg/dl, P < .05). Analysis of the areas under the peripheral concentration curves (60-360 min) showed that the responses of both insulin (52.7 ± 5.6 and 46.5 ± 4.5 pmol · ml−1 300 min1) and C-peptide (252.7 ± 27.5 and 267.0 ± 21.6 pmol · ml−1 · 300 min1) were not significantly different after the oral and 75-g i.v. glucose studies, respectively, whereas in the matching experiment, both the insulin (26.1 ± 3.9 pmol · ml−1 · 300 min−1) and C-peptide (178.0 ± 18.9 pmol ml−1 300 min−1) responses were lower (P < .05) than in the other two studies. Insulin secretory rates were derived from peripheral C-peptide concentrations with an open two-compartment model and individually derived model parameters. The basal insulin secretion rate was 86.8 ± 2.9 pmol/min. The insulin secretory response over the 300 min was 66.2 ± 4.8 nmol after oral glucose. This was similar to that after 75 g i.v. glucose (72.4 ± 4 . 1 nmol), whereas that secreted in response to the matching experiment was lower (47.6 ± 4.1 nmol, P ± .05). As a measure of the clearance of endogenous insulin, the ratio between the area under the insulin secretory curve and the area under the peripheral insulin concentration curve was calculated. This ratio was similar (1906 ± 149 ml/min) during the baseline period and the matching glucose infusion (2042 ± 245 ml/min) but was significantly lower after oral glucose (1330 ±112 ml/min, P < .05). The incretin effect calculated based on the insulin secretion rate (25 ± 9.2%) appeared to be less than if the calculations were based on peripheral insulin levels. These data demonstrate that equivalent doses of glucose administered orally and intravenously elicit an equivalent insulin secretory response. However, when the arterialized plasma glucose curve after 75 g oral glucose is matched by an intravenous glucose infusion, only 35.6 ± 2.9 g glucose was infused, and the intravenous glucose resulted in a lower secretory response. Furthermore, after oral administration of 75 g glucose a significant reduction in insulin clearance resulted. These data provide evidence that the hyperinsulinemia seen after oral glucose is due both to enhanced insulin secretion and diminished insulin clearance.