Article: article from journal or magazin.
Impaired glucose metabolism in the heart of obese Zucker rats after treatment with phorbol ester.
International Journal of Obesity and Related Metabolic Disorders
OBJECTIVE: To investigate the influence of obesity on the regulation of myocardial glucose metabolism following protein kinase C (PKC) activation in obese (fa/fa) and lean (Fa/?) Zucker rats. DESIGN: Isolated hearts obtained from 17-week-old lean and obese Zucker rats were perfused with 200 nM phorbol 12-myristate 13-acetate (PMA) for different time periods prior to the evaluation of PKC and GLUT-4 translocation. For metabolic studies isolated hearts from 48 h starved Zucker rats were perfused with an erythrocytes-enriched buffer containing increased concentrations (10-100 nM) of PMA. MEASUREMENTS: Immunodetectable PKC isozymes and GLUT-4 were determined by Western blots. Glucose oxidation and glycolysis were evaluated by measuring the myocardial release of 14CO2 and 3H2O from [U-14C]glucose and [5-3H]glucose, respectively. RESULTS: PMA (200 nM) induced maximal translocation of ventricular PKCalpha from the cytosol to the membranes within 10 min. This translocation was 2-fold lower in the heart from obese rats when compared to lean rats. PMA also induced a significant translocation of ventricular GLUT-4 from the microsomal to the sarcolemmal fraction within 60 min in lean but not in obese rats. Rates of basal cardiac glucose oxidation and glycolysis in obese rats were approximately 2-fold lower than those of lean rats. Perfusion with increasing concentrations of PMA (10-100 nM) led to a significant decrease of cardiac glucose oxidation in lean but not in obese rats. CONCLUSION: Our results show that in the heart of the genetically obese Zucker rat, the impairment in PKCalpha activation is in line with a diminished activation of GLUT-4 as well as with the lack of PMA effect on glucose oxidation.
Animals, Biological Transport, Biomechanics, Body Weight, Carbon Radioisotopes, Cell Membrane/enzymology, Cytosol/enzymology, Enzyme Activation/drug effects, Female, Glucose/metabolism, Glucose Transporter Type 4, Glycolysis, Heart/physiology, Isoenzymes/metabolism, Kinetics, Monosaccharide Transport Proteins/metabolism, Muscle Proteins, Myocardium/metabolism, Obesity/metabolism, Protein Kinase C/metabolism, Rats, Rats, Zucker, Tetradecanoylphorbol Acetate/pharmacology, Tritium
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