Proteomic analysis reveals cellular pathways regulating carbohydrate metabolism that are modulated in primary human skeletal muscle culture due to treatment with bioactives from Artemisia dracunculus L.

Abstract

Insulin resistance is a major pathophysiologic abnormality that characterizes metabolic syndrome and type 2 diabetes. A well characterized ethanolic extract of Artemisia dracunculus L., termed PMI 5011, has been shown to improve insulin action in vitro and in vivo, but the cellular mechanisms remain elusive. Using differential proteomics, we have studied mechanisms by which PMI 5011 enhances insulin action in primary human skeletal muscle culture obtained by biopsy from obese, insulin-resistant individuals. Using iTRAQ™ labeling and LC-MS/MS, we have identified over 200 differentially regulated proteins due to treatment with PMI 5011 and insulin stimulation. Bioinformatics analyses determined that several metabolic pathways related to glycolysis, glucose transport and cell signaling were highly represented and differentially regulated in the presence of PMI 5011 indicating that this extract affects several pathways modulating carbohydrate metabolism, including translocation of GLUT4 to the plasma membrane. These findings provide a molecular mechanism by which a botanical extract improves insulin stimulated glucose uptake, transport and metabolism at the cellular level resulting in enhanced whole body insulin sensitivity.

Effects of Artemisia dracunculus Aqueous Extract on Blood Sugar, Serum Insulin, Triglyceride and Liver Enzymes in Fructose Drinking Water Male Rats

“…Moreover aqueous extract of Artemisia capillaries has shown a hepatoprotective effects on FFR [10]. Artemisia extract affected on insulin sensitivity, modulating of carbohydrate metabolism and glucose influx [11]. Investigation revealed that Artemisia extracts had shown hepatoprotective and hypolipidemic properties and antioxidative activity in hepatoma cells in Dgalactose-induced oxidative stress in mouse model [12][13][14].…”

Bioactives from Artemisia dracunculus L. enhance insulin sensitivity via modulation of skeletal muscle protein phosphorylation

“…Fifty microgram of protein from each sample was digested with trypsin and labeled with iTRAQ™ labeling reagents as per manufacturer's instructions (AB SCIEX, Foster City, CA) [16]. Briefly, protein extracts in TEAB buffer (2 νg/μL) from each of the four HSkMC samples were denatured using 2% SDS and reduced with 50 mM Tris (2-carboxyethyl) phosphine (TCEP).…”

“…Previous proteomics studies show that PMI 5011 treatment increases abundance of proteins involved in glycolysis pathway and increases glucose uptake and metabolism via enhanced translocation of glucose transporter 4 (GLUT4) into the plasma membrane. Both gel-based and gel-free proteomics analyses also showed that PMI 5011 exhibits anti-inflammatory action by reducing levels of proteins participating in the NFkB pathway [15,16]. As recognized, protein phosphorylation is an important post-translational modification that controls activation and deactivation of proteins and their subcellular localization to regulate metabolic processes.…”

Focus on Proteomics and Bioinformatics in Translational Research and Plant Research of Obesity and Diabetes

“…These proteins were up regulated in diabetic condition and the authors have reported the value of proteomic approach in identifying them also as potential markers for various types of diseases [72]. Proteins involved in regulating inflammatory pathways were obtained from the ethanolic extract of Artemisia dracunculus L. (PMI 5011) using differential proteomics data by Kheterpal et al [73] and Scherp et al 2012 [74]. They have shown that this extract modulates proteins involved in regulating inflammatory pathways and regulate carbohydrate metabolism in human skeletal muscle culture, respectively [73,74].…”

“…Proteins involved in regulating inflammatory pathways were obtained from the ethanolic extract of Artemisia dracunculus L. (PMI 5011) using differential proteomics data by Kheterpal et al [73] and Scherp et al 2012 [74]. They have shown that this extract modulates proteins involved in regulating inflammatory pathways and regulate carbohydrate metabolism in human skeletal muscle culture, respectively [73,74]. Panax ginseng has been used to treat diabetes [75].…”