The physiologic significance of the secretion of endogenous insulin into the portal circulation. I. Comparison of the effects of glucagon-free insulin adminstered via the portal vein and via a peripheral vein on the magnitude of hypoglycemia and peripheral glucose utilization.

The metabolic consequences of exogenous insulin which is administered parenterally may differ from those of the endogenously secreted hormone for at least two reasons: exogenous insulin may be altered in its commercial preparation; its activity may be different because it enters the body through the systemic circulation. Under physiologic conditions, insulin is secreted by the pancreatic betacytotropic cells into the branches of the portal circulation, traversing the liver prior to entry into the systemic circulation where it is bound in a variety of tissues; this binding is apparently intimately associated with insulin activity (1-4). Theoretically, insulin secreted into the portal vein, because it passes directly into the liver, may have a metabolic effect different from insulin administered peripherally: all of the insulin reaches the liver, and may therefore increase the hepatic effect and decrease the peripheral effect (qualitative difference) ; part of the insulin may be destroyed by hepatic insulinase reducing the net amount available (quantitative difference); finally, there may be no significant physiologic alteration by this initial passage through the liver. The purpose of this study was to determine whether the initial passage of insulin through the liver altered its subsequent metabolic activity qualitatively or quantitatively by comparing the effect of glucagon-free insulin 2 administered via the portal and via a peripheral vein on the magnitude of the hypoglycemia and the magnitude of the change in peripheral glucose utilization. The