The purpose of the study was to examine the transhepatic and peripheral effects of somatostatin (SN) infusion on plasma glucose and insulin during insulin (IN) infusion. Hepatic blood flow was measured electromagnetically during intermittent sampling from the portal and hepatic veins, femoral artery, and right external jugular vein. Hepatic blood flow [sum of portal vein (PV) and hepatic artery] was similar during IN or IN + SN infusions. IN concentrations decreased in the portal vein from 374.8 +/- 50.3 to 295.8 +/- 25.9 pM (p less than 0.01) when SN was infused with IN. Hepatic venous plasma IN concentration also decreased from 143.6 +/- 26.6 to 88.3 +/- 10.1 pM (p less than 0.01). Plasma IN concentrations in the femoral artery and jugular vein remained unchanged. Hepatic insulin extraction changed from 64 +/- 4% during IN to 72 +/- 3% during IN + SN (p less than 0.01). Hepatic clearance and total body clearance were unchanged. Peripheral venous glucose with a nadir of 3.82 +/- 0.2 mM during IN alone decreased to a nadir of 3.16 +/- 0.27 mM (p less than 0.01) during IN + SN infusion. Mean portal venous glucose concentrations were 5.0 +/- 0.27 and 3.4 +/- 0.19 mM, respectively (p less than 0.01). In two additional experiments in which endogenous C-peptide concentrations were examined in the portal vein and femoral artery, C-peptide levels were lower during IN + SN compared to IN alone. We conclude that SN used to suppress endogenous insulin secretion increases hepatic insulin extraction, lowers glucose concentrations, and suppresses endogenous C-peptide levels to a greater extent than insulin infusion alone.(ABSTRACT TRUNCATED AT 250 WORDS)