Glucose ingestion in dogs alters the hepatic extraction of insulin. In vivo evidence for a relationship between biologic action and extraction of insulin.

Abstract

Oral glucose (25 g) fed to seven healthy, conscious dogs resulted in an increase in peripheral plasma glucose from 109 +/- 3 to 178 +/- 10 mg/dl. Concurrently serum insulin increased in the portal vein to levels approximately threefold greater than those in the periphery. Hepatic insulin delivery rose from 10.8 +/- 0.7 to 59.0 +/- 19.9 m U/min at 60 min. coincident with an increased hepatic insulin extraction from 3.3 to 41.4 mU/min (corresponding to an increase in hepatic extraction from 31 +/- 4 to 59 +/- 7%), both returning to basal at 3 h. In each animal there was a positive correlation between hepatic insulin delivery and extraction (r = 0.80, P less than 0.001 for the seven experiments combined). These changes in heptic insulin delivery and extraction after glucose metabolism associated with insulin action. As hepatic insulin extraction increased, hepatic glucose output declined, both parameters returning to basal levels by 3 h, indicating a negative correlation between hepatic insulin extraction and hepatic glucose output (r = 0.63, P less than 0.001; n = 7). The factors that mediate this marked and rapidly occurring increase in hepatic insulin extraction after oral glucose are unknown, and may include hepatic insulin delivery, glucose levels in the blood flow, and gut factors released by oral glucose intake. The association of changes in hepatic insulin extraction in vivo with an insulin effect on the liver as measured hepatic glucose output is consistent with in vitro observations relating insulin degradation to receptor binding.