Effect Of Glucose Supplementation On Hypoxia-induced VEGF And PGC-1α Expression In Cardiac Muscle

Abstract

PURPOSE: This study determined whether glucose supplementation affects moderate hypoxia effect on cardiac vascular endothelial growth factor (VEGF) and glucose transporter (GLUT) expressions. The AMPK (AMP activated protein kinase)-PGC-1α (peroxisome proliferator activated receptor co-activator 1α) signaling pathway was also examined. METHODS: Rats were randomly separated into control (N=40) and glucosesupplemented (N=40) groups, and both were subjected to 0, 30, 60, 120, and 240 min of 14% systemic hypoxia. The mRNA levels of glucose transporters, VEGF, and PGC-1α were measured by quantitative real-time PCR. AMP-activated protein kinase (AMPK) phosphorylation (Thr 172) was also determined. RESULTS: Glucose supplementation significantly elevated cardiac glycogen. But GLUT1 and GLUT4 mRNA levels were not significantly altered with hypoxia. VEGF mRNA levels were transiently elevated by moderate hypoxia and returned to basal level within 240 min. PGC-1α was increased with moderate hypoxia only when glucose is available. Glucose supplementation resulted in an earlier and slightly greater hypoxia-induced VEGF expression. Intriguingly, moderate hypoxia lowered Thr 172 phosphorylation of AMPK and suppressed HIF-1α mRNA level, whereas glucose supplementation partially blocked these changes. CONCLUSIONS: the current study demonstrated a significant facilitative effect of glucose supplementation on hypoxia-induced PGC-1α and VEGF expression.