The Monascus metabolite monascin against TNF-α-induced insulin resistance via suppressing PPAR-γ phosphorylation in C2C12 myotubes

Chronic inflammation in muscle tissue causes insulin resistance and type-2 diabetes. Peroxisome proliferator-activated receptor (PPAR) ligands are reported to activate the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, including pioglitazone, which belong to the thiazolidinedione (TZD). Monascin (MS), a Monascus metabolite, has been reported to exert anti-inflammatory activity in our recent study. Therefore, the alleviating mechanism of MS on tumor necrosis factor-alpha (TNF-alpha; 20 ng/mL) induced insulin resistance in C2C12 cells was investigated in this study. Results showed that MS increased the uptake of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG) in C2C12 myotubes. This result was associated with both PPAR-gamma activity and PI3K/Akt pathway caused by MS inhibited p-JNK activity and prevented PPAR-gamma phosphorylation. Moreover, we found that MS may act a PPAR-gamma agonist to improve insulin sensitivity, and this issue was further confirmed by PPAR-gamma antagonist (GW9662). Briefly, MS as pioglitazone, stabilized PPAR-gamma structure and diminished PPAR-gamma phosphorylation thereby improving insulin resistance. (C) 2011 Elsevier Ltd. All rights reserved.