Hepatic extraction of insulin after stimulation of secretion with oral glucose or parenteral nutrients

Abstract

To determine whether hepatic extraction of insulin differs when glucose is administered by parenteral and physiologic routes, we studied responses to oral glucose and to intravenous (IV) infusion of glucose or glucose plus arginine in normal volunteers. As in earlier studies, when IV glucose infusions were empirically programmed to produce isoglycemic responses with 50 or 75 g oral glucose, ratios of integrated areas under concentration curves for immunoreactive C-peptide (CP) to insulin in the plasma were higher with IV than with oral glucose. Mean values ± standard errors for these ratios in paired experiments with 50 g oral glucose were 5.6 ± 0.66 compared with 8.3 ± 1.4 with IV glucose ( P < .03). With 75 g oral glucose, the corresponding values were 4.3 ± 0.38 and 7.8 ± 0.50 ( P < .001). These results suggest that hepatic extraction of insulin is diminished when insulin secretion is potentiated by enteroinsular mechanisms after oral glucose administration. To determine whether this phenomenon is related to the route of administration of glucose or to the enhancement of insulin secretion with oral glucose, programmed IV infusions of glucose were used to elicit excursions of plasma CP similar to those obtained after 50 g oral glucose, and programmed infusions of glucose plus arginine were used to elicit excursions of plasma CP similar to those obtained after 75 g oral glucose. Plasma levels of immunoreactive gastric inhibitory polypeptide (GIP) increased substantially after ingestion of 75 g glucose, but did not change during isoglycemic IV glucose infusions or during IV infusions of glucose plus arginine. Under these conditions, ratios of integrated areas under the concentration curves of CP to immunoreactive insulin (IRI) were not significantly different in either set of studies (5.10 ± 0.56 and 5.35 ± 0.61, 6.06 ± 0.47 and 5.41 ± 0.47, respectively). In these experiments with matching of plasma CP excursions, relative hyperglycemia resulted from IV infusion of glucose alone, but was avoided with IV infusion of glucose plus arginine. The results suggest that decreased hepatic extraction of insulin is associated with higher rates of secretion of the hormone, and indicate that this phenomenon is independent of route of delivery of the nutrient stimulus. It is concluded that modulation of hepatic extraction of insulin should not be regarded as an expression of the enteroinsular axis in response to absorption of glucose from the intestine.