| First Author | Brenachot X | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 1820 |
| PubMed ID | 29180649 | Mgi Jnum | J:257193 |
| Mgi Id | MGI:6106085 | Doi | 10.1038/s41467-017-02074-2 |
| Citation | Brenachot X, et al. (2017) Hepatic protein tyrosine phosphatase receptor gamma links obesity-induced inflammation to insulin resistance. Nat Commun 8(1):1820 |
| abstractText | Obesity-induced inflammation engenders insulin resistance and type 2 diabetes mellitus (T2DM) but the inflammatory effectors linking obesity to insulin resistance are incompletely understood. Here, we show that hepatic expression of Protein Tyrosine Phosphatase Receptor Gamma (PTPR-gamma) is stimulated by inflammation in obese/T2DM mice and positively correlates with indices of inflammation and insulin resistance in humans. NF-kappaB binds to the promoter of Ptprg and is required for inflammation-induced PTPR-gamma expression. PTPR-gamma loss-of-function lowers glycemia and insulinemia by enhancing insulin-stimulated suppression of endogenous glucose production. These phenotypes are rescued by re-expression of Ptprg only in liver of mice lacking Ptprg globally. Hepatic PTPR-gamma overexpression that mimics levels found in obesity is sufficient to cause severe hepatic and systemic insulin resistance. We propose hepatic PTPR-gamma as a link between obesity-induced inflammation and insulin resistance and as potential target for treatment of T2DM. |
