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

• Published in: Diabetes, obesity & metabolism Vol. 16; no. 8; pp. 728 - 738
• Main Authors: Vandanmagsar, B., Haynie, K. R., Wicks, S. E., Bermudez, E. M., Mendoza, T. M., Ribnicky, D., Cefalu, W. T., Mynatt, R. L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-08-2014; Wiley Subscription Services, Inc
• Subjects: Akt; AKT protein; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Obesity Agents - pharmacology; Artemisia - chemistry; Artemisia dracunculus; Artemisia dracunculus L; Beta cells; Body Mass Index; Body weight; Cell culture; Cells, Cultured; chemokines; cytokine signaling; Cytokines; Cytokines - agonists; Cytokines - genetics; Cytokines - metabolism; Diabetes; Diabetes Complications - drug therapy; Diabetes Complications - metabolism; Diabetes Complications - pathology; Diabetes mellitus; Erk1/2; Extracellular signal-regulated kinase; Gene expression; Gene Expression Regulation - drug effects; Humans; Hypoglycemic Agents - pharmacology; IkBα; IL6; Inflammation; Insulin; Insulin Resistance; insulin signaling; IRS1; Kinases; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - immunology; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - pathology; Musculoskeletal system; Myotubes; NF-κB protein; NFkB; Obesity - complications; Obesity - drug therapy; Obesity - metabolism; Obesity - pathology; Overweight; Overweight - complications; Overweight - drug therapy; Overweight - metabolism; Overweight - pathology; Phosphorylation; Phosphorylation - drug effects; Plant Extracts - pharmacology; Plant Leaves - chemistry; PMI 5011; Polymerase chain reaction; Propagation; Protein Processing, Post-Translational - drug effects; Proto-Oncogene Proteins c-akt - agonists; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Signal transduction; Signal Transduction - drug effects; Skeletal muscle; skeletal muscle inflammation; TNF; Erk1/2; PMI 5011; IRS1; Akt; NFkB; chemokines; TNF; Artemisia dracunculus L; skeletal muscle inflammation; IL6; IkBα; insulin signaling; cytokine signaling; cytokines; insulin resistance
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12274

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 TNFα (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 IkBα (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.