Kaneko Michiyo, Bucciarelli Loredana, Hwang Yuying C, Lee Larisee, Yan Shi Fang, Schmidt Ann Marie, Ramasamy Ravichandran
Division of Surgical Science, P&S 17-401, Columbia University Medical Center, 630 West 168th St., New York, NY 10032, USA.
Ann N Y Acad Sci. 2005 Jun;1043:702-9. doi: 10.1196/annals.1333.081.
Cardiovascular disease represents the major cause of morbidity and mortality in patients with diabetes mellitus. The impact of cardiac disease includes increased sensitivity of diabetic myocardium to ischemic episodes and diabetic cardiomyopathy, manifested as a subnormal functional response of the diabetic heart independent of coronary artery disease. In this context, we were to our knowledge the first to demonstrate that diabetes increases glucose flux via the first and key enzyme, aldose reductase, of the polyol pathway, resulting in impaired glycolysis under normoxic and ischemic conditions in diabetic myocardium. Our laboratory has been investigating the role of the polyol pathway in mediating myocardial ischemic injury in diabetics. Furthermore, the influence of the aldose reductase pathway in facilitating generation of key potent glycating compounds has led us to investigate the impact of advanced glycation end products (AGEs) in myocardial ischemic injury in diabetics. The potent impact of increased flux via the aldose reductase pathway and the increased AGE interactions with its receptor (RAGE) resulting in cardiac dysfunction will be discussed in this chapter.
心血管疾病是糖尿病患者发病和死亡的主要原因。心脏病的影响包括糖尿病心肌对缺血发作的敏感性增加以及糖尿病性心肌病，表现为糖尿病心脏的功能反应低于正常水平，且与冠状动脉疾病无关。在此背景下，据我们所知，我们是首个证明糖尿病通过多元醇途径的首个关键酶醛糖还原酶增加葡萄糖通量，从而导致糖尿病心肌在常氧和缺血条件下糖酵解受损的研究团队。我们实验室一直在研究多元醇途径在介导糖尿病患者心肌缺血损伤中的作用。此外，醛糖还原酶途径在促进关键强效糖化化合物生成方面的影响，促使我们研究晚期糖基化终产物（AGEs）对糖尿病患者心肌缺血损伤的影响。本章将讨论通过醛糖还原酶途径增加通量以及AGE与其受体（RAGE）相互作用增加导致心脏功能障碍的强大影响。
