title: Modified Si-Miao-San inhibits inflammation and promotes glucose disposal in adipocytes through regulation of AMP-kinase.
abstract: Modified Si-Miao-San (mSMS) is composed of Rhizoma Coptidis, Cortex Phellodendri, Rhizoma Coptidis Semen Coicis and Atractylodes Rhizome. The prescription is used for the management of diabetes and insulin resistance in the clinic. This study aims to investigate its regulation of glucose disposal in adipocytes. Differentiated 3T3-L1 adipocytes were stimulated with conditioned medium derived from activated macrophages to induce insulin resistance and observed the effects of Mac-CM on insulin-mediated glucose uptake along the insulin receptor substrate-1/PI3K/Akt signaling pathway. Moreover, its regulation of AMPK phosphorylation was also investigated. mSMS enhanced AMPK phosphorylation and promoted basal glucose uptake in adipocytes; mSMS inhibited NF-κB activation by reducing P65 phosphorylation and improved insulin-stimulated IRS-1 tyrosine and Akt phosphorylation, leading to the restoration of insulin-mediated glucose uptake when cells were exposed to inflammatory stimulation. These beneficial effects were diminished in the presence of the AMPK inhibitor compound C. mSMS positively regulated AMPK activity, and this action contributed to improving insulin PI3K signaling by the beneficial regulation of IRS-1 function through inhibition of inflammation in adipocytes.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Jiang-Lin
authors.initials: JL
authors.lastname: Yang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Jun-Lian
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, China. Electronic address: zhongyao440@163.com.
authors.forename: Bao-Lin
authors.initials: BL
authors.lastname: Liu
mesh_terms: D041721:3T3-L1 Cells; D000249:Adenosine Monophosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D031174:Atractylodes; D031742:Coix; D039323:Coptis; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D032102:Phellodendron; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004365:Drugs, Chinese Herbal; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D016328:NF-kappa B; D000249:Adenosine Monophosphate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000263:Adenylate Kinase; D005947:Glucose
keywords: AMP-kinase; Adipocytes; Inflammation; Insulin resistance; Modified Si-Miao-San