Effects of chronic undernutrition on glucose uptake and glucose transporter proteins in rat heart.
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 p85alpha and p85beta 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.
Gavete
M Lucia
ML
Instituto de Bioquímica, Centro Mixto: Consejo Superior de Investigaciones Científicas-Universidad Complutense de Madrid, Facultad de Farmacia, Universidad Complutense, Ciudad Universitaria, 28040 Madrid, Spain.
Agote
Maria
M
Martin
M Angeles
MA
Alvarez
Carmen
C
Escriva
Fernando
F
D000818:Animals; D002458:Cell Fractionation; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins; D009748:Nutrition Disorders / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; C495694:Slc2a4 protein, rat; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose