Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture

作者：Vandanmagsar B; Haynie K R; Wicks S E; Bermudez E M; Mendoza T M; Ribnicky D; Ce**** W T; Mynatt R L^*

来源：DIABETES OBESITY %26 METABOLISM, 2014, 16(8): 728-738.

DOI：10.1111/dom.12274

• Akt
• Artemisia dracunculus L.
• chemokines
• cytokine signaling
• cytokines
• Erk1/2
• IkB beta
• IL6
• insulin resistance
• insulin signaling
• IRS1
• NFkB
• PMI 5011
• skeletal muscle inflammation
• TNF

Aims: Bioactives of Artemisia dracunculus L. (termed PMI 5011) have been shown to improve insulin action by increasing insulin signalling in skeletal muscle. However, it was not known if PMI 5011%26apos;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. %26lt;br%26gt;Methods: Muscle cell cultures derived from lean, overweight and diabetic-obese subjects were used. Expression of pro-inflammatory genes and inflammatory response of human myotubes were evaluated by real-time polymerase chain reaction (RT-PCR). Insulin signalling and activation of inflammatory pathways in human myotubes were evaluated by multiplex protein assays. %26lt;br%26gt;Results: We found increased gene expression of monocyte chemoattractant protein 1 (MCP1) and TNF alpha (tumour necrosis factor alpha), and basal activity of the NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway in myotubes derived from diabetic-obese subjects as compared with myotubes derived from normal-lean subjects. In line with this, 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 with 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 IkBa (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha)-NFkB and moreover, NFkB target gene expression, possibly by preventing further propagation of the inflammatory response within muscle tissue. %26lt;br%26gt;Conclusions: PMI 5011 improved insulin sensitivity in diabetic-obese myotubes to the level of normal-lean myotubes despite the presence of pro-inflammatory cytokines.

• 出版日期2014-8
• 单位rutgers