The physiologic significance of portal vs. peripheral injection of insulin in man.

The site and rate of entry of insulin into the body may affect its metabolic actions. This study tested for the first time in man the hypothesis that the mode of action of endogenous insulin differs from peripherally injected insulin. In 11 nondiabetic and six diabetic patients we compared the effects on peripheral glucose utilization (PGU) and degree of hypoglycemia of the following: (1) glucagon-free insulin rapidly injected and slowly infused into the portal circulation via percutaneous splenic puncture; (2) peripheral intravenous inslin; (3) peripheral intravenous sodium tolbutamide. The arteriovenous glucose difference (A-V) and (A-V)/A ratios were calculated as parameters for measuring PGU. In nondiabetics our experiments showed: (1) similar magnitudes of hypoglycemia for insulin given by both routes, and (2) a significantly smaller (A-V)/A and therefore PGU, after the intraportal route, particularly after a slow infusion. Intravenous tolbutamide produced marked hypoglycemia and a small PGU comparable to that of slow intraportal infusion of insulin. In diabetics, results were similar. These findings suggest that, compared to the action of peripherally administered insulin, intraportally injected exogenous insulin or tolbutamide-induced endogenous insulin has a greater hepatic and a lesser peripheral effect on glucose metabolism.