PEDF increases GLUT4-mediated glucose uptake in rat ischemic myocardium via PI3K/AKT pathway in a PEDFR-dependent manner

International Journal of Cardiology
Yanliang YuanZhongming Zhang

Abstract

Targeted increase in glucose uptake of ischemic myocardium is a potential therapeutic strategy for myocardial ischemia. PEDF presents a profound moderating effect on glucose metabolism of cells, but its role is still controversial. Here, we try to demonstrate the direct effect of PEDF on glucose uptake in ischemic myocyte and to elucidate its underlying mechanism. Lentivirus vectors carrying PEDF gene were delivered into the myocardium to locally overexpress PEDF in a myocardial ischemia/reperfusion rat model. PET imaging showed that PEDF local overexpression increased [18F]-FDG uptake of ischemic myocardium. In vitro, PEDF directly increased the glucose uptake in hypoxic cardiomyocytes. The expression of glucose transporter 4 (GLUT4) on plasma membrane of hypoxic cardiomyocytes was significantly upregulated by PEDF, but its total amount was not changed. The increased glucose uptake and cardioprotective effects induced by PEDF were blocked by the GLUT4 inhibitor indinavir. PEDF-mediated GLUT4 translocation and glucose uptake increase in hypoxic cardiomyocytes were prevented by phosphatidyl-inositol-3 kinase (PI3K) inhibitor or AKT inhibitor. The PEDF-mediated glucose uptake was also diminished when PEDF receptor (PEDFR) was dow...Continue Reading

Citations

Nov 26, 2019·Free Radical Research·Naomi BrookCrispin R Dass
Dec 29, 2020·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Xichun QinZhongming Zhang
Dec 5, 2020·World Journal of Biological Chemistry·Tiannan WangGuo-Xun Chen

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