Possible Involvement of Kinins and Prostaglandins in the Translation of Insulin Action on Glucose Uptake into Skeletal Muscle

Abstract

Recent evidence suggesting that endogenous liberation of kinins from kininogen by kininogenases is essential for the well known increase of glucose uptake occuring during muscle work (1) and hypoxia (2) and the fact that kinins exhibit a molecular weight similar to that ascribed to the “Muscle Activity Factor” (3), points to the possibility that kinins themselves represent the required mediator. The earlier finding that the factor liberated during hypoxia accelerated glucose uptake as insulin via enhanced transport across the cell membrane (4,5) and kinins themselves exhibited insulin-like activity in normal (6) and diabetic man (7) implied that kinins might share with insulin its mechanism of action. Since, furthermore, evidence had been obtained that the effect of kinins on glucose uptake into muscle was mediated via synthesis of prostaglandins (8) it was of interest to investigate whether kinins and prostaglandins are involved in insulin action. In order to answer this question we studied the action of insulin on glucose uptake into skeletal muscle tissue of the human forearm (9,19) under conditions where endogenous liberation of kinins was prevented by infusion of a kallikrein inhibitor (10,23) and endogenous biosynthesis of prostaglandins was prevented by indomethacin pretreatment (11).