Role of cannabinoids and the endocannabinoid system in modulation of diabetic cardiomyopathy

Figure 3 Role of cannabinoid receptors in inflammation. Activation of toll-like receptor 4 induces tumor necrosis factor receptor associated factor 6, which activates transforming growth factor beta-activated kinase 1 (TAK1), phosphoinositide 3-kinase (PI3K), and mitogen-activated protein kinase signaling. This will induce the formation of nuclear factor-kappa B (NF-κB) and the subsequent increase in inflammatory cytokines levels such as interleukin 6 (IL-6), IL-1β, and tumor necrosis factor α (TNF-α) in addition to the activation of inducible nitric oxide synthase (iNOS) and monocyte chemoattractant ptotein-1 (MCP-1). Stimulation of cannabinoid receptors will increase the PI3K activity leading to increased activity of protein kinase B (Akt/PKB), which in turn enhances the nuclear translocation of NF-κB. TLR4: Toll-like receptor 4; TRAF6: Tumor necrosis factor receptor associated factor 6; PI3K: Phosphoinositide 3-kinase; MAPK: Mitogen-activated protein kinase; NF-κB: Nuclear factor-kappa B; IL: Interleukin; TNF-α: Tumor necrosis factor α; MCP-1: Monocyte chemoattractant protein-1.