The Monascus metabolite monascin against TNF-α-induced insulin resistance via suppressing PPAR-γ phosphorylation in C2C12 myotubes
Journal
Food and Chemical Toxicology
Journal Volume
49
Journal Issue
10
Pages
2609-2617
Date Issued
2011
Author(s)
Abstract
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-α (TNF-α; 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-γ activity and PI3K/Akt pathway caused by MS inhibited p-JNK activity and prevented PPAR-γ phosphorylation. Moreover, we found that MS may act a PPAR-γ agonist to improve insulin sensitivity, and this issue was further confirmed by PPAR-γ antagonist (GW9662). Briefly, MS as pioglitazone, stabilized PPAR-γ structure and diminished PPAR-γ phosphorylation thereby improving insulin resistance. ? 2011 Elsevier Ltd.
Subjects
Monascin (MS); Peroxisome proliferator-activated receptor (PPAR); Phosphorylation; Pioglitazone; Tumor necrosis factor-α (TNF-α)
SDGs
Other Subjects
monascin; natural product; peroxisome proliferator activated receptor gamma; phosphatidylinositol 3 kinase; pioglitazone; protein kinase B; stress activated protein kinase; tumor necrosis factor alpha; unclassified drug; animal cell; article; controlled study; drug mechanism; enzyme activity; insulin resistance; insulin sensitivity; Monascus; mouse; myotube; nonhuman; protein phosphorylation; 4-Chloro-7-nitrobenzofurazan; Animals; Blotting, Western; Cell Line; Deoxyglucose; Heterocyclic Compounds, 3-Ring; Insulin Resistance; Mice; Monascus; Muscle Fibers, Skeletal; Phosphatidylinositol 3-Kinases; Phosphorylation; PPAR gamma; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha; Monascus
Type
journal article