Effects of chronic undernutrition on glucose uptake and glucose transporter proteins in rat heart

Abstract

The high energy demands of myocardium are met through the metabolism of lipids and glucose. Importantly, enhanced glucose utilization rates are crucial adaptations of the cardiac cell to some pathological conditions, such as hypertrophy and ischemia, but the effects of undernutrition on heart glucose metabolism are unknown. Our previous studies have shown that undernutrition increases insulin-induced glucose uptake by skeletal muscle. Consequently, we considered the possibility of a similar adaptation in the heart. With this aim, undernourished rats both in the basal state and after euglycemic hyperinsulinemic clamps were used to determine the following parameters in myocardium: glucose uptake, glucose transporter (GLUT) content, and some key components of the insulin signaling cascade. Heart membranes were prepared by subcellular fractionation in sucrose gradients. Although GLUT-4, GLUT-1, and GLUT-3 proteins and GLUT-4/1 mRNAs were reduced by undernutrition, basal and insulin-stimulated 2-deoxyglucose uptake were significantly enhanced. Phosphoinositol 3-kinase activity remained greater than control values in both conditions. The abundance of p85α and p85β regulatory subunits of phosphoinositol 3-kinase was increased as was phospho-Akt during hyperinsulinemia. These changes seem to improve the insulin stimulus of GLUT-1 translocation, as its content was increased at the surface membrane. Such adaptations associated with undernutrition must be crucial to improvement of cardiac glucose uptake.