Hepatitis C virus induced insulin resistance impairs response to anti viral therapy

Figure 2 Interaction between hepatitis C virus core, insulin- and interferon-α signaling pathways continuous lines represent activation. Dotted lines represent inhibition. Hepatitis C virus core protein induces expression of tumour necrosis α (TNF-α), which in turn activates suppressor of cytokines-3 (SOCS-3). Activation of SOCs-3 leads to proteasomal degradation of insulin receptor substrate and inactivates phosphatidyl-inositol-3-kinase (PI3K), leading to inhibition of translocation of glucose transferase (GLUT-4) to cell membrane, blocking intracellular glucose entry, with subsequent hyperglycemia, hyperinsulinemia and peripheral insulin resistance. Activation of SOCS-3 also leads leading to inhibition of Tyr-phosphorylation of signal transducers and activators of transcription 1 leading to impaired TNF-α signaling. HCV: Hepatitis C virus; IFNAR2c: Interferon receptor chain 2; IRS2: Insulin receptor substrate 2; JAK: Janus kinase; TYK2: Tyrosine kinase 2; STAT: Signal transducer and activator of transcription.