title: Jinlida reduces insulin resistance and ameliorates liver oxidative stress in high-fat fed rats.
abstract: BACKGROUND
  Jinlida (JLD) is a compound preparation formulated on the basis of traditional Chinese medicine and is officially approved for the treatment of type 2 diabetes (T2DM) in China. We aimed to elucidate the mechanism of JLD treatment, in comparison to metformin treatment, on ameliorating insulin sensitivity in insulin resistant rats and to reveal its anti-oxidant properties.
  
  
  METHODS
  Rats were fed with standard or high-fat diet for 6 weeks. After 6 weeks, the high-fat fed rats were subdivided into five groups and orally fed with JLD or metformin for 8 weeks. Fasting blood glucose (FBG), fasting blood insulin, blood lipid and antioxidant enzymes were measured. Intraperitoneal glucose tolerance test (IPGTT) and hyperinsulinemic euglycemic clamp technique were carried out to measure insulin sensitivity. Gene expression of the major signaling pathway molecules that regulate glucose uptake, including insulin receptor (INSR), insulin receptor substrate-1 (IRS-1), phosphoinositide-3-kinase (PI3K), protein kinase beta (AKT), and glucose transporter type 2 (GLUT2), were assessed by quantitative RT-PCR. The totle and phosphorylation expression of IRS-1, AKT, JNK and p38MAPK were determined by Western blot.
  
  
  RESULTS
  Treatment with JLD effectively ameliorated the high-fat induced hyperglycemia, hyperinsulinemia and hyperlipidemia. Similar to metformin, the high insulin resistance in high-fat fed rats was significantly decreased by JLD treatment. JLD displayed anti-oxidant effects, coupled with up-regulation of the insulin signaling pathway. The attenuation of hepatic oxidative stress by JLD treatment was associated with reduced phosphorylation protein levels of JNK and p38MAPK.
  
  
  CONCLUSIONS
  Treatment with JLD could moderate glucose and lipid metabolism as well as reduce hepatic oxidative stress, most likely through the JNK and p38MAPK pathways.
authors.affiliation: Department of Internal Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Clinical medicine, Shandong University, Jinan 250012, Shandong Province, China.
authors.forename: An
authors.initials: A
authors.lastname: Song
authors.affiliation: Department of Internal Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zang
authors.affiliation: Department of Clinical Medical Research Center and Geriatric Key Laboratory, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China; Department of Endocrinology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China. Electronic address: sguangyao2@163.com.
authors.forename: Guangyao
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Endocrinology, Bethune International Peace Hospital, Shijiazhuang 050000, Hebei Province, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Duan
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004041:Dietary Fats; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; C000601818:jinlida; D008687:Metformin
keywords: Antioxidant; Diabetes; Jinlida; Liver; Oxidative stress; Traditional Chinese medicine