Morel Sandrine, Berthonneche Corinne, Tanguy Stéphane, Toufektsian Marie-Claire, Perret Pascale, Ghezzi Catherine, de Leiris Joël, Boucher François
Laboratoire Nutrition, Vieillissement et Maladies Cardiovasculaires, IFRT Ingénierie pour le Vivant, Université Joseph Fourier, Grenoble, France.
Mol Cell Biochem. 2005 Apr;272(1-2):9-17. doi: 10.1007/s11010-005-4778-1.
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.
与未发生胰岛素抵抗的受试者相比，具有高胰岛素分泌能力的糖尿病前期受试者患心血管疾病的风险加倍。心肌增加其糖酵解ATP生成的能力在决定缺血条件下的细胞存活中起着关键作用，这一点已得到充分证实。到目前为止，糖尿病前期状态是否通过影响心脏通过糖酵解增加能量生成的能力来降低心脏对缺血的耐受性仍不清楚。本研究的目的是评估胰岛素抵抗是否会影响心肌在缺血条件下增加糖酵解的能力。给雄性Wistar大鼠喂食富含果糖（33%）的饮食8周以诱导糖尿病前期状态。分离心脏并进行离体低流量（2%）缺血30分钟。与对照组相比，果糖饮食在基础条件下增加了心肌细胞中肌膜GLUT4的定位。这种作用并未伴随着葡萄糖利用的增加。缺血诱导对照组中GLUT4向质膜转运，但在糖尿病前期心脏中并未显著改变这些转运蛋白的分布。与对照组相比，果糖喂养的大鼠心脏在缺血条件下的糖酵解通量显著降低。果糖喂养的大鼠心脏在缺血期间糖酵解通量的降低并非由于己糖激酶II下游的代谢抑制，因为未检测到葡萄糖-6-磷酸在心脏中的积累。总之，我们的结果表明，糖尿病前期状态通过降低糖酵解通量适应性来降低心肌对缺血的耐受性。
