title: A polyphenol rescues lipid induced insulin resistance in skeletal muscle cells and adipocytes.
abstract: Skeletal muscle and adipose tissues are known to be two important insulin target sites. Therefore, lipid induced insulin resistance in these tissues greatly contributes in the development of type 2 diabetes (T2D). Ferulic acid (FRL) purified from the leaves of Hibiscus mutabilis, showed impressive effects in preventing saturated fatty acid (SFA) induced defects in skeletal muscle cells. Impairment of insulin signaling molecules by SFA was significantly waived by FRL. SFA markedly reduced insulin receptor β (IRβ) in skeletal muscle cells, this was affected due to the defects in high mobility group A1 (HMGA1) protein obtruded by phospho-PKCε and that adversely affects IRβ mRNA expression. FRL blocked PKCε activation and thereby permitted HMGA1 to activate IRβ promoter which improved IR expression deficiency. In high fat diet (HFD) fed diabetic rats, FRL reduced blood glucose level and enhanced lipid uptake activity of adipocytes isolated from adipose tissue. Importantly, FRL suppressed fetuin-A (FetA) gene expression, that reduced circulatory FetA level and since FetA is involved in adipose tissue inflammation, a significant attenuation of proinflammatory cytokines occurred. Collectively, FRL exhibited certain unique features for preventing lipid induced insulin resistance and therefore promises a better therapeutic choice for T2D.
authors.affiliation: Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, Napaam, Sonitpur, Assam, India.
authors.forename: Bhaskarjyoti
authors.initials: B
authors.lastname: Gogoi
authors.affiliation: Department of Zoology, School of Life Science, Visva-Bharati University, Santiniketan 731235, West Bengal, India.
authors.forename: Priyajit
authors.initials: P
authors.lastname: Chatterjee
authors.affiliation: Department of Zoology, School of Life Science, Visva-Bharati University, Santiniketan 731235, West Bengal, India.
authors.forename: Sandip
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, Napaam, Sonitpur, Assam, India; Dibrugarh University, National Highway 37, Dibrugarh 786004, Assam, India.
authors.forename: Alak Kumar
authors.initials: AK
authors.lastname: Buragohain
authors.affiliation: Department of Zoology, School of Life Science, Visva-Bharati University, Santiniketan 731235, West Bengal, India.
authors.forename: Samir
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, Napaam, Sonitpur, Assam, India. Electronic address: suman@tezu.ernet.in.
authors.forename: Suman
authors.initials: S
authors.lastname: Dasgupta
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D003373:Coumaric Acids / Q000302:isolation & purification / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D005227:Fatty Acids / Q000009:adverse effects; D005786:Gene Expression Regulation; D025741:HMGA1a Protein / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D031584:Hibiscus / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D018515:Plant Leaves / Q000737:chemistry; D011401:Promoter Regions, Genetic; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D060749:alpha-2-HS-Glycoprotein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D003373:Coumaric Acids; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D060749:alpha-2-HS-Glycoprotein; D025741:HMGA1a Protein; C004999:ferulic acid; D011972:Receptor, Insulin; D051744:Protein Kinase C-epsilon
keywords: Ferulic acid; Fetuin-A; Insulin receptor; Insulin resistance; PKCε; SFA