Insulin Resistance and Skin Diseases

Figure 1

Insulin signalling pathway: insulin binds to the insulin receptor leading to its autophosphorylation and recruitment of adaptor molecules such as insulin receptor substrates (IRS 1–6) to engage multiple downstream signalling pathways. IRS activation can be also triggered by IGF-1 signalling. Phosphoinositide 3-kinase (PI3-K)/Akt, mammalian target of rapamycin (mTOR), and the Ras/mitogen-activated protein kinase (MAPK) pathways represent the major cellular signalling pathways activated. Particularly, AKT controls the assembly of glucose transporter- (GLUT-) 4 at the cell membrane and thus controls glucose influx into the cell. mTOR complex 1 (mTORC1) activates the kinase S6K1, which phosphorylates and inhibits IRS and thus reduces AKT-GLUT-dependent glucose uptake, the principal mechanism of peripheral insulin resistance. AKT phosphorylation pathway inhibits FOXO-1 mediated gene expression by its extrusion from the nucleus to the cytoplasm, preventing FOXO-1 mediated repression of androgen receptors. GSK-3 = glycogen synthase kinase 3 and FOXO-1 = forkhead box protein O-1.