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Early pre-diabetic state alters adaptation of myocardial glucose metabolism during ischemia in rats

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Abstract

Pre-diabetic subjects with high insulin secretory capacity have double risk of cardiovascular disease compared with subjects who do not develop insulin-resistance. It is well established that the ability of the myocardium to increase its glycolytic ATP production plays a crucial role in determining cell survival under conditions of ischemia. Up to now, whether the pre-diabetic state reduces the tolerance of the heart to ischemia by affecting its ability to increase its energy production through glycolysis remains unknown. The aim of the present study was to assess whether insulin resistance affects the ability of the myocardium to increase glycolysis under ischemic conditions. Male Wistar rats were fed for 8 weeks a fructose-enriched (33%) diet to induce a pre-diabetic state. Hearts were isolated and subjected to ex-vivo low-flow (2%) ischemia for 30 min. The fructose diet increased sarcolemmal GLUT4 localisation in myocardial cells under basal conditions compared with controls. This effect was not accompanied by increased glucose utilisation. Ischemia induced the translocation of GLUT4 to the plasma membrane in controls but did not significantly modify the distribution of these transporters in pre-diabetic hearts. Glycolytic flux under ischemic conditions was significantly lower in fructose-fed rat hearts compared with controls. The reduction of glycolytic flux during ischemia in fructose-fed rat hearts was not due to metabolic inhibition downstream hexokinase II since no cardiac accumulation of glucose-6-phosphate was detected. In conclusion, our results suggest that the pre-diabetic state reduces the tolerance of the myocardium to ischemia by decreasing glycolytic flux adaptation.

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Authors and Affiliations

  1. Laboratoire Nutrition, Vieillissement et Maladies Cardiovasculaires, IFRT Ingénierie pour le Vivant, Université Joseph Fourier, Grenoble, France

    Sandrine Morel, Corinne Berthonneche, Marie-Claire Toufektsian, Joël de Leiris & François Boucher

  2. Laboratoire des Adaptations Cardiovasculaires à l’Exercice, Université d’Avignon et des Pays de Vaucluse, Avignon, France

    Stéphane Tanguy

  3. Radiopharmaceutiques Biocliniques, INSERM E0340, IFRT Ingénierie pour le Vivant, Université Joseph Fourier, Grenoble, France

    Pascale Perret & Catherine Ghezzi

  4. Domaine de la Merci, Bâtiment Jean Roget, Université Joseph Fourier, Laboratoire NVMC EA 3746, IFRT 130 Ingénierie pour le Vivant, 38706, La Tronche, France

    François Boucher

Authors
  1. Sandrine Morel
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  2. Corinne Berthonneche
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  3. Stéphane Tanguy
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  4. Marie-Claire Toufektsian
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  5. Pascale Perret
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  6. Catherine Ghezzi
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  7. Joël de Leiris
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  8. François Boucher
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Correspondence to François Boucher.

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Morel, S., Berthonneche, C., Tanguy, S. et al. Early pre-diabetic state alters adaptation of myocardial glucose metabolism during ischemia in rats. Mol Cell Biochem 272, 9–17 (2005). https://doi.org/10.1007/s11010-005-4778-1

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  • DOI: https://doi.org/10.1007/s11010-005-4778-1

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