Figure 3
From: Bench-to-bedside review: Glucose and stress conditions in the intensive care unit
Role of hypoxia in cell metabolic reprogramming. Hypoxia-inducible factors (HIFs), O2-sensing transcription factors, regulate the transcription of genes encoding Heme-oxygenase-1 (HO-1), erythropoietin (EPO), and numerous molecules involved in vascular reactivity (such as nitric oxide synthase (NOS)), recruitment of endothelial progenitors, and cytoprotection through angiogenic growth factors such as vascular endothelial growth factor (VEGF). During hypoxia, glycogenolysis is stimulated, increasing glucose availability. An increase in glucose transporter (GLUT) expression enables augmented glucose uptake. This overexpression of GLUTs is mediated by the activation of AMP kinase (AMPK) and p38 mitogen-activated kinase. Stimulation of AMPK results from a decreased cytoplasmic ATP/AMP ratio together with altered cellular redox status. Phosphofructokinase-1 and lactate dehydrogenase activity is stimulated by increased lactate production. HIF decreases mitochondrial oxygen consumption and induces the expression of pyruvate dehydrogenase kinase, the main inhibitor of pyruvate dehydrogenase and of the entry of acetylCoA into mitochondria. Adapted from [36]. OXPHOS, oxidative phosphorylation; TGF, transforming growth factor.