Stimulation of Cardiac Glucose Transport by Thioctic Acid and Insulin

Abstract

Thioctic acid (alpha-lipoic acid) has been shown to improve insulin-regulated glucose disposal in animal models of insulin resistance and type 2 diabetic patients. In the present study, we have used isolated adult ventricular cardiomyocytes in order to analyze 1) direct effects of this compound on glucose uptake in a primary muscle cell, and 2) the interaction with the insulin signalling cascade. Both insulin and thioctic acid (2.5 mM) induced a rapid increase in 3-O-methylglucose transport to 322+/-43 and 385+/-58 (n = 5) percent of basal control, respectively. Combined stimulation did not result in an additional significant increase in the transport rate. Preincubation of cardiomyocytes with the phosphatidylinositol 3-kinase inhibitor wortmannin completely abolished the effects of insulin and thioctic acid, whereas gamma-linolenic acid selectively blocked the effect of this compound. These data show that thioctic acid mimics insulin action by activating the signalling cascade at or before the level of phosphatidylinositol 3-kinase.