Fig. 1

Inflammatory adipokines suppress insulin signaling resulting in insulin resistance. IRS1/2 phosphorylated on specific tyrosine residues activates the phosphatidyl inositol 3-kinase (PI3K)-AKT/protein kinase B (PKB) pathway and Ras-mitogen-activated protein kinase (MAPK) pathway. PI3K-AKT signaling pathway regulates metabolic processes such as glucose uptake(muscle and adipocytes), glycogen synthesis (muscle and liver), protein synthesis(muscle and liver), and gluconeogenesis (liver). Inflammatory signals, TNF-a, IL-6, Leptin and saturated free fatty acid, activate inhibitory molecules such as SOCS and JNK to suppress insulin signaling resulting in insulin resistance. PI3K-dependent PDK1 activation is negatively regulated by phospholipid phosphatases such as phosphatase and tensin homolog (PTEN) that degrade PIP3 [86]. doi: 10.3389/fendo.2013.00071, Reproduced with permission Frontiers in Endocrinology)