title: Rosmarinic Acid Mediates Mitochondrial Biogenesis in Insulin Resistant Skeletal Muscle Through Activation of AMPK.
abstract: Rosmarinic acid (RA), a polyphenol, is known to improve hepatic insulin sensitivity in experimental type 2 diabetes. However, its effect on skeletal muscle insulin resistance is meagerly understood. The present study was aimed to investigate the up- and downstream mediators of the molecular targets of RA in attenuating insulin resistance in the skeletal muscle both in vivo and in vitro. We found that supplementation of RA increased the expression of key genes involved in the mitochondrial biogenesis like PGC-1α, SIRT-1, and TFAM via activation of AMPK in the skeletal muscle of insulin resistant rats as well as in L6 myotubes. Further, RA treatment increased the glucose uptake and decreased the phosphorylation of serine IRS-1 while increasing the translocation of GLUT 4. Together, our findings evidenced that RA treatment significantly inhibit insulin resistance in skeletal muscle cells by enhancing mitochondrial biogenesis. J. Cell. Biochem. 118: 1839-1848, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Division of Molecular Biology, Interdisciplinary Institute of Indian System of Medicine, SRM University, Kattankulathur, Kancheepuram 603203, Tamil Nadu, India.
authors.forename: Govindaraj
authors.initials: G
authors.lastname: Jayanthy
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India.
authors.forename: Vellai
authors.initials: V
authors.lastname: Roshana Devi
authors.affiliation: Division of Molecular Biology, Interdisciplinary Institute of Indian System of Medicine, SRM University, Kattankulathur, Kancheepuram 603203, Tamil Nadu, India.
authors.forename: Kaliappan
authors.initials: K
authors.lastname: Ilango
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India.
authors.forename: Sorimuthu Pillai
authors.identifier: 0000-0001-5137-3956
authors.initials: SP
authors.lastname: Subramanian
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides / Q000494:pharmacology*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D001678:Organelle Biogenesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000097123:Rosmarinic Acid
chemical_list: D055372:AMP-Activated Protein Kinases; D002934:Cinnamates; D053630:Depsides; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D056564:Sirtuin 1; D014157:Transcription Factors; D000097123:Rosmarinic Acid; C526296:Irs1 protein, rat; C501429:Ppargc1a protein, rat; C489030:Tfam protein, rat; C488368:Sirt1 protein, rat
keywords: INSULIN RESISTANCE; MITOCHONDRIAL BIOGENESIS; ROSMARINIC ACID; SKELETAL MUSCLE; TYPE 2 DIABETES