Inflammation and insulin resistance

Abstract 

Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and the Metabolic syndrome. In this review, we focus on the interconnection between obesity, inflammation and insulin resistance. Pro-inflammatory cytokines can cause insulin resistance in adipose tissue, skeletal muscle and liver by inhibiting insulin signal transduction. The sources of cytokines in insulin resistant states are the insulin target tissue themselves, primarily fat and liver, but to a larger extent the activated tissue resident macrophages. While the initiating factors of this inflammatory response remain to be fully determined, chronic inflammation in these tissues could cause localized insulin resistance via autocrine/paracrine cytokine signaling and systemic insulin resistance via endocrine cytokine signaling all of which contribute to the abnormal metabolic state.

Abbreviations: T2DM, type 2 diabetes mellitus, MetS, metabolic syndrome, TNF, tumor necrosis factor, CRP, C-reactive protein, PKC, protein kinase C, PI3K, phosphatidylinositol 3-kinase, PKB, protein kinase B, MAPK, mitogen activated protein kinase, IRS, insulin receptor substrate, IKKb, I kappa B kinase beta, JNK1, C-jun N-terminal kinase 1, DIO, diet-induced obesity, HFD, high fat diet, ER, endoplasmic reticulum, Mcp1, monocyte chemoattractant protein 1, Ccr2, chemokine receptor 2, FFA, free fatty acids, NO, nitric oxide, iNOS, inducible nitric oxide synthase, Pparg, peroxisome proliferator activated receptor gamma

Keywords: Insulin resistance, Inflammation, Cytokines, Macrophage