The Journal of Japanese College of Angiology
Online ISSN : 1880-8840
Print ISSN : 0387-1126
ISSN-L : 0387-1126
Review Article
New Insight into the Regulation of Glucose Metabolism in the Pathophysiology of Ischemic Heart Diseases
Tomohisa NagoshiMichihiro Yoshimura
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2020 Volume 60 Issue 8 Pages 127-134


Although glucose becomes an important preferential substrate for cardiac metabolism in ischemic heart diseases, insulin resistance (IR), a prominent feature in diabetes, impairs myocardial glucose utilization, leading to an energy deficiency state in ischemic myocardium. Recent large-scale clinical trials have shown that SGLT2-inhibitors reduce cardiovascular events in diabetic patients. However, the functional significance of cardiac SGLTs compared with those of other glucose transporters (insulin-dependent GLUT4 is the major isoform) remain incompletely understood. We found that GLUT4 expression was reduced in high-fat-diet (HFD)-induced obese mice hearts both at baseline and in response to ischemia-reperfusion, whereas in contrast, SGLT1 expression was maintained constant during ischemia-reperfusion regardless of diet conditions. SGLT2 was not detected in the hearts of any mice. After ischemia-reperfusion, cardiac function was impaired in HFD, associated with reduction in myocardial glucose uptake, probably due to blunted GLUT4 response. Although non-selective SGLT-inhibitor, phlorizin, impaired cardiac functional recovery in normal-diet mice, further impaired functional recovery with dramatically increased infarct size and reduction in glucose uptake were observed in HFD. A series of our recent studies suggested that cardiac SGLT1 (but not SGLT2) plays a compensatory protective role via enhanced glucose utilization, particularly under IR condition, in which stress-induced GLUT4 upregulation is compromised.

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この記事はクリエイティブ・コモンズ [表示 - 非営利 - 改変禁止 4.0 国際]ライセンスの下に提供されています。
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