Somatostatin increases hepatic insulin extraction

Somatostatin has been widely employed in studies of hepatic metabolism to suppress the endogenous secretion of the pancreatic hormones, insulin and glucagon. The possibility of somatostatin having hepatic effects has been considered before, but not decisively demonstrated. Eleven anesthetized dogs were used to assess the effect of somatostatin on hepatic insulin extraction (HIE) and hepatic glucose production (HGP). Insulin was infused by peripheral vein alone and during somatostatin (800 ng/kg/hr) in one series (I) of experiments and in the reverse sequence in another series (II). Portal vein and hepatic artery blood flow were measured electromagnetically, and blood samples were taken from the hepatic artery, portal vein, hepatic vein and a peripheral vein. HIE was increased in the presence of insulin plus somatostatin infusion. The combined results in Series I and II were 72.0 +/- 3.0% compared in insulin alone (64.0 +/- 4.0%, p less than 0.01). HGP was decreased in the presence of insulin and somatostatin infusion compared to insulin infusion alone both in Series I and II (1.71 +/- 0.25 to 3.72 +/- 4.0%, combined results, p less than 0.01). Whether this reduction in HGP indicates a direct effect of somatostatin on the liver, in addition to the inhibition of glucagon secretion, remains to be clarified. However, a decrease in hepatic glucose production is consistent with increased insulin extraction during somatostatin observed in the present study. We conclude that somatostatin increases the hepatic extraction of exogenous insulin. This effect of somatostatin is associated with decreased hepatic glucose production.