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Impaired glucose metabolism in the heart of obese Zucker rats after treatment with phorbol ester

International Journal of Obesity volume 26, pages 327–334 (2002)Cite this article

Abstract

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 PKCα 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 PKCα activation is in line with a diminished activation of GLUT-4 as well as with the lack of PMA effect on glucose oxidation.

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Acknowledgements

The authors sincerely thank Professor B Jeanrenaud for the generous gift of Zucker rats. We also thank Dr lsabelle Cusin for valuable discussion. We gratefully acknowledge the expert technical assistance of Irene Papageorgiou (metabolic studies), Christine Gerber and Manuella Rey (PKC and GLUT-4 studies). This study was supported by grant nos 31-42295.94 and 31-52935.97 from the Swiss National Science Foundation.

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Authors and Affiliations

  1. Division of Endocrinology and Diabetology, Department of Internal Medicine, University Hospital of Geneva, Geneva, Switzerland

    D Morabito, MB Vallotton & U Lang

  2. Department of Internal Medicine, Cardiology Center, University of Geneva, Geneva, Switzerland

    C Montessuit, N Rosenblatt-Velin & R Lerch

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  1. D Morabito
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  2. C Montessuit
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  3. N Rosenblatt-Velin
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  4. R Lerch
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Correspondence to U Lang.

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Morabito, D., Montessuit, C., Rosenblatt-Velin, N. et al. Impaired glucose metabolism in the heart of obese Zucker rats after treatment with phorbol ester. Int J Obes 26, 327–334 (2002). https://doi.org/10.1038/sj.ijo.0801881

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