The Effect of Insulin and Growth Hormone on the Flux of Tracer from Labelled Lactate in Perfused Rat Heart

Abstract

l[2.14C]Lactate tracer was added at 30 min to the perfused rat‐heart preparation described in the previous paper. The specific activities of perfusate and tissue lactate and pyruvate were measured over the period up to 60 min. Perfusate and heart lactate radioactivity equilibrated rapidly: not so perfusate and heart pyruvate. No pyruvate was lost from the tissue: the sole precursor of perfusate pyruvate was lactate. In the presence of insulin all pyruvate taken up from perfusate was obligatorily reduced to lactate. A proportion of pyruvate in the heart did not become labelled and there is good reason to believe this is not an artifact. Rate parameters at different steps in pyruvate metabolism have been determined by computer modelling. Both hormones modify these parameters: in particular pyruvate dehydrogenase appears to undergo rapid 7‐fold activation. The rate of exchange of label between lactate and intracellular labelled pyruvate was used to calculate the [NAD]/[NADH] ratios in the exchange compartment and in mitochondria. Both hormones reduced the ratio about 5 times by comparison with control. The results emphasise the disparity between perfusate lactate/pyruvate ratio and the redox potential of cardiac cytoplasm. The data strongly support the compartmentization in more than one distinct cytoplasmic space of some glycolytic enzymes in cardiac tissue. The relationship of these “compartments” to heart morphology is briefly discussed. Evidence is presented that growth hormone exerts a much greater rapid “insulin‐like” effect than has hitherto been suspected. Copyright © 1973, Wiley Blackwell. All rights reserved