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. 2021 Aug 20;13(8):e17321. doi: 10.7759/cureus.17321

Figure 1. Summary of the inflammatory pathways affecting hepatic insulin resistance in NAFLD.

Figure 1

Insulin activates its receptor, which results in tyrosine phosphorylation of the IRS1 and IRS2 and activation of downstream effector pathways, including the PI3K-phosphoinositide-dependent kinase-AKT and the RAS-ERK pathways. Pro-inflammatory signaling or reactive oxygen species can activate IKK-β. The activated NF-kB is then translocated into the nucleus and binds to specific deoxyribonucleic acid response elements. Inflammatory cytokines such as interleukin-6 promote insulin resistance by inducing SOCS1 and SOCS3. SOCS1 and SOCS3 impair insulin signaling through ubiquitin-dependent degradation of IRS. The JNK, or mitogen-activated protein kinase, represents another important inhibitory kinase of IRS that is activated in response to a variety of extracellular stimuli and cellular stressors such as oxidative and ER stress

ER: endoplasmic reticulum; JNK: c-Jun N-terminal kinase; IKK-β: IkappaB kinase beta; SOCS: suppressor of cytokine signaling; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; AP-1: activator protein 1; IRS1: insulin receptor substrate 1; IRS2: insulin receptor substrate 2; PI3K: phosphatidylinositol 3-kinase; AKT: protein kinase B; RAS: rat sarcoma; ERK1/2: extracellular-signal-regulated kinase 1/2

Copyright/license: this figure is from an open-access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). No modifications were made to the original figure

Fujii H, Kawada N, Japan Study Group Of Nafld J-N: The role of insulin resistance and diabetes in nonalcoholic fatty liver disease. Int J Mol Sci. 2020, 21:3863. 10.3390/ijms21113863 [18]