Figure 6. Insulin resistance and inflammation in diabetes type 2. Insulin binds to insulin receptor (IR) in insulin sensitive tissues, and autophosphorylates tyrosine molecules of IRS-1 and -2 substrates. In the presence of obesity, and hyperlipidemia, the influx of free fatty acids, inflammatory cytokines and glucose activates IKKβ and JNK, which are the mediators for stress and inflammatory. In turn IKKβ and JNK inhibit tyrosine phosphorylation of IRS1 and 2 and promote transcriptional activation of genes related to inflammatory and stress responses resulting in insulin resistance. [Modified by Berbudi et al (133)]. IRS 1 -2, insulin receptor substrates; ER, Endoplasmic reticulum; IKKβ, inhibitory kappa B kinase β; JNK1 and c-Jun N-terminal kinase I.