title: Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver.
abstract: This study was performed to investigate the molecular mechanism and the therapeutic effect of berberine on nonalcoholic fatty liver disease (NAFLD). Rat models were given a high-fat diet (42% kcal) until they developed NAFLD, then were given normal saline (n=10), berberine (n-=10) at 187.5mg/kg/day, or pioglitazone (n=10) at 10.0mg/kg/day intragastrically for 4 weeks, respectively, and evaluated by hyperinsulinemic euglycemic clamping for insulin sensitivity. Serum biochemical markers and liver triglyceride (TG) were analyzed, real-time RT-PCR for mRNA expression and western blotting for protein expression of insulin receptor (IR) and insulin receptor substrate-2 (IRS-2) in liver tissues were performed, and hepatic histopathology in the rat models with NAFLD at the end of treatment was compared with normal controls (n=10). The NAFLD rats developed insulin resistance, showing increased fasting blood glucose and insulin levels, decreased glucose infusion rate, increased weight of epididymal fat (g/100g body weight), obvious hepatic steatosis and inflammation, and down-regulated IRS-2 mRNA and protein levels compared with normal controls (all P<0.05). In comparison with those treated with saline, model rats treated with berberine or pioglitazone underwent significant recovery, including up-regulated IRS-2 mRNA and protein (all P<0.05). Our results indicate that berberine may improve insulin resistance of NAFLD by up-regulating mRNA and protein levels of IRS-2, a key molecule in the insulin signaling pathway, suggesting that berberine may be used to treat NAFLD.
authors.affiliation: Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, China.
authors.forename: Lian-Jun
authors.initials: LJ
authors.lastname: Xing
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Hua
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Zheng
authors.forename: Guang
authors.initials: G
authors.lastname: Ji
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D005234:Fatty Liver / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics* / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D007004:Hypoglycemic Agents; D055504:Insulin Receptor Substrate Proteins; D012333:RNA, Messenger; D001599:Berberine; D011972:Receptor, Insulin