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Preconditioning affords cardioprotection through PI3K‐Akt mediated myocardial glucose uptake during early reperfusion
Author(s) -
Ji Lele,
Liu Wenchong,
Fu Feng,
Cai Xiaoqing,
Yang Weidong,
Wang Jing,
Zhang Haifeng,
Gao Feng
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1033.14
Subject(s) - cardioprotection , glut4 , glucose transporter , protein kinase b , wortmannin , pi3k/akt/mtor pathway , glucose uptake , medicine , ischemic preconditioning , glycogen synthase , insulin , chemistry , pharmacology , phosphorylation , endocrinology , cardiology , ischemia , signal transduction , biochemistry
Objective This study was designed to investigate whether ischemic preconditioning (IPC) afforded cardioprotection through transition of increased myocardial glucose utilization and the underlying “switch” mechanism. Methods IPC was achieved by 2 cycles of 5‐min occlusion and 5‐min reperfusion. Myocardial glucose uptake was assessed with 18 F‐2‐deoxy‐2‐fluoro‐D‐glucose. Results IPC improved cardiac functional recovery and reduced myocardial injury following myocardial ischemia/reperfusion (MI/R) ( P <0.05). Cardiac glucose uptake was markedly elevated after IPC treatment (17.0±1.5 vs. 12.4±1.0 in MI/R, P <0.05, n=10–12), together with the increase in translocation of glucose transporter 4 (GLUT4) to cardiomyocyte membrane ( P <0.01). Meanwhile, myocardial PI3K expression, Akt and glycogen synthase kinase (GSK)‐3β phosphorylation were all significantly enhanced in IPC group ( P <0.05). Wortmannin not only abrogated the cardioprotection of IPC, but also inhibited IPC‐stimulated GLUT4 translocation. Moreover, the cardioprotection of IPC was markedly blunted in STZ‐induced diabetic hearts with decreased IPC‐induced GLUT4 translocation and PI3K‐Akt‐GSK‐3β signaling ( P <0.05, n=6). Conclusions IPC‐induced transition of myocardial substrate uptake from fatty acids to glucose via insulin‐dependent PI3K/Akt signaling contributes to IPC‐induced cardioprotection.