Insulin resistance in diabetes: The promise of using induced pluripotent stem cell technology

Figure 1 Schematic illustration of insulin signaling pathways. Insulin binding activates the insulin receptor (INSR), which enables the recruitment of insulin receptor substrate isoforms and subsequent activation of the phosphatidylinositol 3-kinase (PI3K). The downstream event of PI3K enhances glucose uptake by translocation of glucose transporter proteins over cell membrane, enhances glycogen, lipid and protein synthesis and regulates lipolysis and gluconeogenesis. Alternative pathway for glucose transporter type 4 (GLUT-4) translocation by insulin stimulation. Insulin binding activates the INSR, which enables F binding to Cbl associated protein phosphorylates Cbl and recruit CrkII/C3G complex. This complex converts guanosine diphosphate into guanosine triphosphate (GTP) on TC10. The stimulated GTP containing TC10 involved in GLUT-4 translocation by actin remodeling on GLUT-4. INSR: Insulin receptor; IRS: Insulin receptor substrate; PI3K: Phosphatidylinositol 3-kinase; PIP2: Phosphatidylinositol 4,5 bisphosphate; PIP3: Phosphatidylinositol 3,4,5 trisphosphate; PDK1: Phosphatidylinositide dependent protein kinase 1; aPKC: Atypical protein kinase C; GSK3: Glycogen synthase kinase 3; FoxO: Forkhead box O; mTORC: mTOR complex; AS160: Akt substrate 160kDa; F: Flotillin; CAP: Cbl associated protein; C3G: Guanine nucleotide exchange factor; GTP: Guanosine triphosphate; GDP: Guanosine diphosphate; GLUT-4: Glucose transporter type 4.