1. Early pre-diabetic state alters adaptation of myocardial glucose metabolism during ischemia in rats
- Author
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Stéphane Tanguy, Catherine Ghezzi, Joël de Leiris, Corinne Berthonneche, Sandrine Morel, Marie-Claire Toufektsian, Pascale Perret, François Boucher, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Physiopathologie des adaptations cardiovasculaires à l'Exercice, Avignon Université (AU), Radiopharmaceutiques biocliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine, Yale University School of Medicine, Physiologie cardio-Respiratoire Expérimentale Théorique et Appliquée (TIMC-IMAG-PRETA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), and Sandrine Morel was supported by grant from Fédération Française de Cardiologie and Merck-Lipha
- Subjects
Male ,pre-diabetic state ,MESH: Glycogen ,Clinical Biochemistry ,Myocardial Ischemia ,Muscle Proteins ,MESH: Myocytes, Cardiac ,030204 cardiovascular system & hematology ,Sarcolemma ,0302 clinical medicine ,MESH: Diabetes Mellitus, Experimental ,Myocytes, Cardiac ,MESH: Animals ,Glycolysis ,Hexosephosphates ,MESH: Sarcolemma ,0303 health sciences ,Glucose Transporter Type 4 ,MESH: Hexosephosphates ,General Medicine ,glycolysis ,Adaptation, Physiological ,3. Good health ,MESH: Glucose ,Protein Transport ,MESH: Insulin Resistance ,MESH: Monosaccharide Transport Proteins ,MESH: Glycolysis ,MESH: Myocardial Ischemia ,glucose extraction ,Glycogen ,MESH: Protein Transport ,medicine.medical_specialty ,MESH: Myocardium ,Monosaccharide Transport Proteins ,MESH: Rats ,Clinical chemistry ,Ischemia ,Fructose ,ischemia ,In Vitro Techniques ,Carbohydrate metabolism ,Biology ,Diabetes Mellitus, Experimental ,MESH: Prediabetic State ,Prediabetic State ,MESH: Muscle Proteins ,03 medical and health sciences ,Insulin resistance ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Internal medicine ,medicine ,Animals ,Lactic Acid ,Rats, Wistar ,Molecular Biology ,030304 developmental biology ,Myocardium ,MESH: Rats, Wistar ,Cell Biology ,medicine.disease ,MESH: Adaptation, Physiological ,MESH: Male ,Rats ,Glucose ,Endocrinology ,Basal (medicine) ,biology.protein ,GLUT4 translocation ,MESH: Lactic Acid ,MESH: Glucose Transporter Type 4 ,Insulin Resistance ,MESH: Fructose ,Flux (metabolism) ,GLUT4 - Abstract
International audience; 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.
- Published
- 2005