THE PHYSIOLOGICAL SIGNIFICANCE OF THE SECRETION OF ENDOGENOUS INSULIN INTO THE PORTAL CIRCULATION. III. EVIDENCE FOR A DIRECT IMMEDIATE EFFECT OF INSULIN ON THE BALANCE OF GLUCOSE ACROSS THE LIVER*†

Abstract

Insulin was administered by slow intravenous infusion in 18 dogs with complete end-to-side portacaval shunts to determine whether insulin has a direct effect on the net balance of glucose across the liver. This preparation was chosen since the portacaval shunt completely separates the liver from the extra-hepatic splanchnic tissues and thereby permits measurement of hepatic rather than splanchnic glucose metabolism. Hepatic blood flow was measured by the hepatic venous catheter technique of Bradley. Whenever insulin was administered in a manner which minimized or prevented the counter-regulatory response to hypoglycemia, hepatic glucose output declined significantly and could account for the greater part of the decrease in the glucose pool. When, on the other hand, insulin was administered by rapid intravenous injection hepatic glucose output increased most likely because of stimulation of the counterregulatory mechanisms by hypoglycemia. These data show that insulin administered under physiologic circumstances produces its blood glucose lowering effect in large part by decreasing the hepatic glucose output. This effect of insulin can be obscured by profound hypoglycemia which elicits a prompt counterregulatory response thereby resulting in an increased hepatic glucose output characteristic of these counterregulatory hormones.