The effect of somatostatin on the hepatic extraction of insulin and glucagon in the anesthetized dog.

Effects of somatostatin (250 ng/kg . min) or saline infusion on hepatic extraction of endogenous and exogenous insulin and glucagon were investigated in anesthetized dogs. After a 20-min control period, somatostatin or saline was infused into the superior mesenteric vein for 100 min. During the final 50 min of the somatostatin or saline infusion, insulin (1.7 mU/kg . min) and glucagon (20 ng/kg . min) were also infused. These infusions were then replaced with a saline infusion for an additional 30 min. Somatostatin rapidly and significantly decreased portal vein insulin and glucagon concentrations. Hepatic extraction of endogenous insulin decreased from the control value of 61 +/- 5% to 29 +/- 10% during the final 20 min of somatostatin infusion before exogenous insulin and glucagon were added to the infusion. The decrease in hepatic extraction of endogenous insulin is based on the mean of the individual values of the eight dogs in the group and may be spurious because of the very low concentrations of insulin which were being measured and the fact that at such low concentrations, some dogs appeared to have negative hepatic extraction of inulin. Glucagon extraction was unchanged (9 +/- 6% compared to 7 +/- 12%) during the first 50 min of infusion of somatostatin. Column chromatography demonstrated that the 3500 mol wt fraction of glucagon comprised 75 +/- 4% of the total glucagon immunoreactivity in the portal vein during the control period and 67 +/- 13% during the infusion of somatostatin. During the final 20 min of somatostatin infusion before the addition of insulin and glucagon, the blood glucose significantly decreased and hepatic glucose output fell from 2.4 +/- 0.4 to 1.4 +/- 0.3 mg/kg . min. However, the insulin to glucagon (3500 mol wt fraction) molar ratio did not change significantly (4.2 +/- 1.1 to 2.6 +/- 0.5). During the final 20 min of the combined infusion of somatostatin, insulin, and glucagon, hepatic extraction of insulin returned to control values and glucagon extraction rose from 7 +/- 12% to 35 +/- 11%. Hepatic glucose output increased without any significant change in the portal vein insulin to glucagon molar ratio. After the termination of the combined infusion, hepatic extraction of insulin was unchanged, but glucagon removal returned to control values. At this time, the portal vein insulin to glucagon ratio rose, and hepatic production of glucose fell below control values. These results demonstrate that somatostatin may influence peripheral insulin and glucagon values by modifying their hepatic extraction and inhibiting their pancreatic secretion. Hepatic glucose output did not always reflect the portal vein insulin to glucagon molar ratio.