PMID- 24521217 OWN - NLM STAT- MEDLINE DCOM- 20150330 LR - 20211021 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 16 IP - 8 DP - 2014 Aug TI - Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture. PG - 728-38 LID - 10.1111/dom.12274 [doi] AB - 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'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. 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. RESULTS: We found increased gene expression of monocyte chemoattractant protein 1 (MCP1) and TNFalpha (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 IkBalpha (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. CONCLUSIONS: PMI 5011 improved insulin sensitivity in diabetic-obese myotubes to the level of normal-lean myotubes despite the presence of pro-inflammatory cytokines. CI - (c) 2014 John Wiley & Sons Ltd. FAU - Vandanmagsar, B AU - Vandanmagsar B AD - Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA. FAU - Haynie, K R AU - Haynie KR FAU - Wicks, S E AU - Wicks SE FAU - Bermudez, E M AU - Bermudez EM FAU - Mendoza, T M AU - Mendoza TM FAU - Ribnicky, D AU - Ribnicky D FAU - Cefalu, W T AU - Cefalu WT FAU - Mynatt, R L AU - Mynatt RL LA - eng GR - R01DK089641/DK/NIDDK NIH HHS/United States GR - P30 DK072476/DK/NIDDK NIH HHS/United States GR - 8P20GM103528/GM/NIGMS NIH HHS/United States GR - R01 DK098687/DK/NIDDK NIH HHS/United States GR - P20 GM103528/GM/NIGMS NIH HHS/United States GR - P50 AT002776/AT/NCCIH NIH HHS/United States GR - P50AT002776/AT/NCCIH NIH HHS/United States GR - 2P30-DK072476/DK/NIDDK NIH HHS/United States GR - R01 DK089641/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140310 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Anti-Obesity Agents) RN - 0 (Cytokines) RN - 0 (Hypoglycemic Agents) RN - 0 (PMI-5011) RN - 0 (Plant Extracts) RN - EC 2.7.11.1 (AKT1 protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology MH - Anti-Obesity Agents/pharmacology MH - Artemisia/*chemistry MH - Body Mass Index MH - Cells, Cultured MH - Cytokines/agonists/genetics/metabolism MH - Diabetes Complications/drug therapy/metabolism/pathology MH - Gene Expression Regulation/drug effects MH - Humans MH - Hypoglycemic Agents/*pharmacology MH - *Insulin Resistance MH - Muscle Fibers, Skeletal/*drug effects/immunology/metabolism/pathology MH - Obesity/complications/drug therapy/metabolism/pathology MH - Overweight/complications/drug therapy/metabolism/pathology MH - Phosphorylation/drug effects MH - Plant Extracts/*pharmacology MH - Plant Leaves/chemistry MH - Protein Processing, Post-Translational/drug effects MH - Proto-Oncogene Proteins c-akt/agonists/antagonists & inhibitors/genetics/metabolism MH - Signal Transduction/*drug effects PMC - PMC4107009 MID - NIHMS568342 OTO - NOTNLM OT - Akt OT - Artemisia dracunculus L OT - Erk1/2 OT - IL6 OT - IRS1 OT - IkBalpha OT - NFkB OT - PMI 5011 OT - TNF OT - chemokines OT - cytokine signaling OT - cytokines OT - insulin resistance OT - insulin signaling OT - skeletal muscle inflammation COIS- Conflict of interest The authors declare no potential conflicts of interest relevant to this article. Conflict of interest details: Design: Vandanmagsar B., Mynatt R.L. Conduct/data collection: Vandanmagsar B., Bermudez E., Mendoza T., Ribnicky D. Analysis: Vandanmagsar B., Cefalu W., Mynatt R.L. Writing manuscript: Vandanmagsar B., Haynie K., Wicks S., Mynatt R.L. Authorship details: Vandanmagsar B: no conflict of interest Haynie K: no conflict of interest Wicks S: no conflict of interest Bermudez E: no conflict of interest Mendoza T: no conflict of interest Ribnicky D: no conflict of interest Cefalu W: no conflict of interest Mynatt R: no conflict of interest EDAT- 2014/02/14 06:00 MHDA- 2015/03/31 06:00 PMCR- 2015/08/01 CRDT- 2014/02/14 06:00 PHST- 2013/11/08 00:00 [received] PHST- 2013/12/09 00:00 [revised] PHST- 2014/02/06 00:00 [accepted] PHST- 2014/02/14 06:00 [entrez] PHST- 2014/02/14 06:00 [pubmed] PHST- 2015/03/31 06:00 [medline] PHST- 2015/08/01 00:00 [pmc-release] AID - 10.1111/dom.12274 [doi] PST - ppublish SO - Diabetes Obes Metab. 2014 Aug;16(8):728-38. doi: 10.1111/dom.12274. Epub 2014 Mar 10.