Original Articles Direct and Indirect Effects of Insulin on Glucose Uptake and Storage by the Liver

Studies were conducted in conscious 42-h–fasted dogs to determine how much of insulin’s effect on hepatic glucose uptake arises from its direct hepatic action versus its indirect (extrahepatic) action. Each experi-ment consisted of equilibration, basal, and experimen-tal periods. During the latter, somatostatin, basal intraportal glucagon, portal glucose (21.3 mol kg1 min1), and peripheral glucose (to double the hepatic glucose load) were infused. During the experimental period, insulin was infused intraportally at a basal rate (BI, n 6), at a fourfold basal rate (PoI, n 6), or via a peripheral vein to create a selective increase in the arterial insulin level similar to that in PoI (PeI, n 6). Arterial and hepatic sinusoidal insulin levels (in pico-moles per liter) during the experimental period wer