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Bioactives of Artemisia dracunculus L. ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture (LB333)
Author(s) -
Vandanmagsar Bolormaa,
Haynie Kimberly,
Wicks Shawna,
Bermudez Estrellita,
Mendoza Tamra,
Ribnicky David,
Cefalu William,
Mynatt Randall
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb333
Subject(s) - medicine , endocrinology , skeletal muscle , insulin resistance , protein kinase b , myogenesis , insulin , insulin receptor , inflammation , proinflammatory cytokine , phosphorylation , biology , microbiology and biotechnology
Obesity‐associated, low‐grade, systemic inflammation is major contributor to obesity‐induced insulin resistance. Impaired insulin signalling in skeletal muscle is a key feature of type 2 diabetes. Bioactives of Artemisia dracunculus L. (termed PMI 5011) have been shown to improve insulin action by increasing insulin signalling in skeletal muscle. However, it has not known if PMI 5011’s effects are retained during an inflammatory condition. We examined the attenuation of insulin action and whether PMI 5011 enhances insulin signalling in the inflammatory environment with elevated cytokines. We found increased inflammation in skeletal muscle tissue of diet‐induced obese mice with upregulated Mcp1, Tnfα, Cxcl5, Cxcl10 and Tnfr1, Tnfr2 gene expressions. In line with this we detected increases in gene expression of MCP1 and TNFα, and basal activity of the NFkB pathway in myotubes derived from diabetic‐obese subjects as compared to myotubes derived from normal‐lean subjects. Multiplex protein analysis revealed that basal Akt phosphorylation (Ser473) was significantly higher, while insulin‐stimulated phosphorylation of Akt (Ser473) was lower in myotubes from normal‐overweight and diabetic‐obese subjects compared to normal‐lean subjects. PMI 5011 treatment reduced basal phosphorylation of Akt and enhanced insulin‐stimulated phosphorylation of Akt in the presence of cytokines in human myotubes. PMI 5011 treatment led to an inhibition of cytokine‐induced activation of inflammatory signalling pathways such as Erk1/2 and IkBα‐NFkB and moreover, NFkB target gene expression, possibly by preventing further propagation of the inflammatory response within muscle tissue. Thus PMI 5011 improved insulin sensitivity in diabetic‐obese myotubes to the level of normal‐lean myotubes despite the presence of pro‐inflammatory cytokines. Grant Funding Source : Supported by grants NCAMM (P50AT002776 NIH), ADA (1‐10‐BS‐129), NIH (RO1DK089641), COBRE (NIH 8P20GM103528), NORC (NIH 2P30‐DK072476)