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

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; 20ng/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.

• Authors: Bao-Hong Lee, Wei-Hsuan Hsu, Te-Han Liao, Tzu-Ming Pan
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 49 Issue 10 Pg. 2609-17 (Oct 2011) ISSN: 1873-6351 [Electronic] England
• PMID: 21777645 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Heterocyclic Compounds, 3-Ring
• PPAR gamma
• Tumor Necrosis Factor-alpha
• Deoxyglucose
• 4-Chloro-7-nitrobenzofurazan
• 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose
• monascin

Topics

• 4-Chloro-7-nitrobenzofurazan (analogs & derivatives, pharmacokinetics)
• Animals
• Blotting, Western
• Cell Line
• Deoxyglucose (analogs & derivatives, pharmacokinetics)
• Heterocyclic Compounds, 3-Ring (pharmacology)
• Insulin Resistance
• Mice
• Monascus (chemistry)
• Muscle Fibers, Skeletal (drug effects, metabolism)
• PPAR gamma (genetics, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation (drug effects)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, metabolism, pharmacology)