Figures & data
Notes: Current information suggests that insulin activates INSR to stimulate the phosphorylation of multiple tyrosine residues in the IRS and promote diverse biological responses. Illustrated here is the response of stimulation of glucose transport into muscle and fat cells. Activation of TLR4 by fatty acids initiates intracytoplasmic signals that activate the JNK–AP-1 and IKK–NFκB axes which in turn increase the expression of cytokine-encoding genes. Cytokines initiate the hepatic production of APPs (eg, CRP, fibrinogen, haptoglobin, etc.) and dysregulate the INSR-IRS-mediated glucose transport into promoting serine phosphorylation of IRS that in turn reduces its tyrosine phosphorylation and, thereby, disrupts the insulin action.
Abbreviations: AKT, protein kinases B (PKB); AP-1, activator protein-1; APPs, acute phase proteins; G, glucose; GLUT4, glucose tansporter-4; I, insulin; IKK, inhibitor of NFκB kinase-β; IL-1β and -6, interleukin-1 β and -6; INSR, insulin receptor; IRAK1 and 4, interleukin-1 receptor-associated kinase 1 and 4; IRS, insulin substrate; JNK, c-Jun amino-terminal kinase; MyD88, myeloid differentiation primary response gene-88; NFκB, nuclear factor κ B; PI3K, phosphoinositide-3 kinase. PI(3,4,5)P3, Phosphatidylinositol 3,4,5-trisphosphate. PKC, protein kinase C. TAB, TAK binding protein. TAK1, mitogen-activated protein kinase kinase kinase (MAPKKK). TLR4, toll-like receptor-4; TNFα, tumor necrosis factor-α; TRAF6, TNF receptor-associated factor 6.
Abbreviations: AKT, protein kinases B (PKB); AP-1, activator protein-1; APPs, acute phase proteins; G, glucose; GLUT4, glucose tansporter-4; I, insulin; IKK, inhibitor of NFκB kinase-β; IL-1β and -6, interleukin-1 β and -6; INSR, insulin receptor; IRAK1 and 4, interleukin-1 receptor-associated kinase 1 and 4; IRS, insulin substrate; JNK, c-Jun amino-terminal kinase; MyD88, myeloid differentiation primary response gene-88; NFκB, nuclear factor κ B; PI3K, phosphoinositide-3 kinase. PI(3,4,5)P3, Phosphatidylinositol 3,4,5-trisphosphate. PKC, protein kinase C. TAB, TAK binding protein. TAK1, mitogen-activated protein kinase kinase kinase (MAPKKK). TLR4, toll-like receptor-4; TNFα, tumor necrosis factor-α; TRAF6, TNF receptor-associated factor 6.
Note: Depicted are the increases or decreases (see text) in relative values of various inflammatory markers and disease factors that take place as overweight progresses towards T2DM.
Abbreviations: CRP, C-reactive protein; FFA, free fatty acids; IGT, impaired glucose tolerance; IL, interleukin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; TG, triglycerides; T2DM, type 2 diabetes mellitus.
Abbreviations: CRP, C-reactive protein; FFA, free fatty acids; IGT, impaired glucose tolerance; IL, interleukin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; TG, triglycerides; T2DM, type 2 diabetes mellitus.