Major signaling mechanisms mediating GLUT4 translocation in muscle and/or adipose tissues: insulin (red and green), ischemia/exercise or contraction (blue) stimulated GLUT4 translocation. For insulin signaling cascade, PI3-kinase-dependent (green) and independent (red) pathways are described. APS, adapter protein with Pleckstrin homology and Src homology 2 domains; CAP, c-Cbl-associated protein; Cbl, Casitas B-lineage Lymphoma; Crk, v-crk avian sarcoma virus CT10 oncogene homolog; IRS1, Insulin receptor substrate 1; PI3K, phosphoinositide 3-kinase; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol 3,4,5-triphosphate; PDK1, 3-phosphoinositide dependent protein kinase-1; Protein kinase B, Akt; AS160, Akt substrate of 160 kDa; aPKC, atypical protein kinase C; LKB1, liver kinase B1; CaMKK, calcium/calmodulin-dependent protein kinase kinase; AMPK, 5′ AMP-activated protein kinase; PKD, protein kinase D; NOS, nitric oxide synthase; NO, nitric oxide.