The physiological role of p53 protein in the prevention of cancer development through blocking cell cycle progression, regulating cellular senescence or apoptosis is well established. In recent years though, the emerging role of p53 in metabolic regulation has been a topic of great interest. Not only p53 is activated by stress signals, it also seems to complexly control energy metabolism under normal conditions. By regulating gene expression and other indirect means p53 participates in the regulation of glucose, fatty acid, amino acid (glutaminolysis) and purine metabolism, influences mitochondrial integrity and oxidative phosphorylation, insulin sensitivity, antioxidant response, autophagy and mammalian Target of Rapamycin (mTOR) signalling to name a few. Importantly, p53 induces expression of TP53-Induced Glycolysis And Apoptosis Regulator (TIGAR) which stimulates Pentose Phosphate Pathway (PPP) with subsequent production of reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH) necessary for reduction of glutathione thus supporting an efficient antioxidant defence. Activation of PPP is especially relevant in diabetes where it may have protective effect counteracting the negative consequences of hyperglycaemia. PPP can process glucose intermediates accumulating due to hyperglycaemia that activate metabolic pathways largely responsible for the development and progression of microvascular diabetic complications.

Copyright: © 2014 Kuricova K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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