Figure 2 Candidate signalling pathways of irisin in myocytess

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Figure 2 Candidate signalling pathways of irisin in myocytess Figure 2 | Candidate signalling pathways of irisin in myocytes. Irisin can activate the AMP-activated protein kinase (AMPK) pathway by reducing intracellular ATP levels, or by increasing reactive oxygen species (ROS) or intracellular calcium concentrations. Activation of the AMPK pathway stimulates the expression of GLUT4 (also known as SLC2A4), HK2 and PPARA genes and inhibits the expression of PYGM and PCK1 (also known as PEPCKC). The high expression of GLUT4 and HK2, combined with the increased translocation of GLUT4 protein from the cytoplasm to the membrane (mainly via the p38 mitogen-activated protein kinase (MAPK) pathway), induces glucose uptake by myocytes. Conversely, inhibition of PYGM and PCK1 expression reduces glycogenolysis and gluconeogenesis. In addition, the increased expression of PPARA stimulates lipid metabolism. The irisin–AMPK pathway also increases fatty acid β-oxidation. Finally, irisin stimulates biogenesis in mitochondria by regulating the expression of PPARA and TFAM genes and of UCP3 protein. Perakakis, N. et al. (2017) Physiology and role of irisin in glucose homeostasis Nat. Rev. Endocrinol. doi:10.1038/nrendo.2016.221