Figure 2.

Inflammation influences beta cell function and insulin sensitivity. (1) A westernized diet induces insulin resistance and a pro-inflammatory immune response in metabolic active tissues. T cells (Th1 via IFN-γ and CD8+ T cells) have been discussed a secondary mediator that led to the attraction of macrophages, which are the main source of several pro-inflammatory cytokines. (2) An active pro-inflammatory response in those tissues enhances and deteriorates the extend of the insulin resistance via several inflammatory mediators (TNF, IL-6, and IL-1β), mainly secreted from M1 macrophages. Several downstream molecules (JNK, IKK, and SOCS3) interfere with the insulin signaling. Inhibition of those pro-inflammatory pathways led to improvement of insulin sensitivity and glucose tolerance (e.g., pharmacological treatments such as anakinra, gevokizumab, and aspirin). Anti-inflammatory cytokines such as IL-10 (expressed by various immune cell types, but mainly M2 macrophages) and adiponectin (from adipocytes) can resolve inflammation and improve insulin sensitivity. (3) Chronic high concentrations of pro-inflammatory cytokines lead to alpha cell expansion and beta cell dysfunction in pancreatic islets, which drives the progression toward T2D in obese subjects. Th, T helper cell; IFN, interferon; CD, cluster of differentiation; TNF, tumor necrosis factor; IL, interleukin; JNK, c-Jun N-terminal kinases; IKK, IκB kinase; SOCS, suppressor of cytokine signaling; GLUT, glucose transporter; IR, insulin receptor; IRS, insulin response substrate; MCP, monocyte chemoattractant protein 1.