Mechanisms of impaired glucose oxidation and enhanced glycolysis in RVH. In RVH, PDK and HIF-1 are activated. Activation of HIF-1 transactivates many glycolytic genes and also inhibits oxidative metabolism by increasing PDK expression. The interaction of HIF-1 and PDK constitutes a positive feedback mechanism to inhibit PDH and mitochondria respiration. Activation of AMPK enhances activation of GLUT4 and consequently glucose uptake, thereby supporting the glycolytically dependent RV in RVH. Both AMPK and HIF-1 activation depress K+ channel activity.
Additional keywords: glycolysis,glucose,oxidation,anaerobic,HIF-1alpha