title: A refined-JinQi-JiangTang tablet ameliorates prediabetes by reducing insulin resistance and improving beta cell function in mice.
abstract: BACKGROUND
  Refined-JQ (JQ-R) is a mixture of refined extracts from three major herbal components of JinQi-JiangTang tablet: Coptis chinensis (Ranunculaceae), Astragalus membranaceus (Leguminosae), and Lonicera japonica (Caprifoliaceae). Our previous studies have indicated that JQ-R could decrease fasting blood glucose levels in diabetic mice and insulin resistance mice. Investigating the hypoglycemic effect of JQ-R on prediabetes has practical application value for preventing or delaying insulin resistance, impaired glucose tolerance and possibly the development of clinical diabetes.
  
  
  METHODS
  The anti-diabetic potential of JQ-R was investigated using a high fat-diet (HFD)-induced obesity mouse model. C57BL/6J mice (HFD-C57 mice) were fed with high-fat diet for 4 months. HFD-C57 mice were treated with either JQ-R (administered intragastrically once daily for 4 weeks) or metformin (as positive control), and the effects of JQ-R on body weight, blood lipids, glucose metabolism, insulin sensitivity, and beta cell function were monitored.
  
  
  RESULTS
  The body weight, serum cholesterol, and the Homeostasis Model Assessment ratio (insulin resistance index) were significantly reduced in JQ-R or metformin-treated mice, and the glucose tolerance was enhanced and insulin response was improved simultaneously. Moreover, both JQ-R and metformin could activate liver glycogen syntheses even under a relatively high glucose loading. Although glyconeogenesis was inhibited in the metformin treated mice, it was not observed in JQ-R treated mice. Similar to metformin, JQ-R could also improve the glucose infusion rate (GIR) in hyperglycemic clamp test. JQ-R was also shown to increase the levels of phosphorylated AMPKα and phosphorylated acetyl CoA carboxylase (ACC), similar to metformin.
  
  
  CONCLUSIONS
  JQ-R could reduce HFD-induced insulin resistance by regulating glucose and lipid metabolism, increasing insulin sensitivity through activating the AMPK signaling pathway, and subsequently improving β cell function. Therefore, JQ-R may offer an alternative in treating disorders associated with insulin resistance, such as prediabetes and T2DM.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, PR China.
authors.forename: Li-hui
authors.initials: LH
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, PR China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, PR China.
authors.forename: Shuai-nan
authors.initials: SN
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, PR China.
authors.forename: Zhi-yu
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, PR China.
authors.forename: Cai-na
authors.initials: CN
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, PR China.
authors.forename: Su-juan
authors.initials: SJ
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, PR China.
authors.forename: Lin-yi
authors.initials: LY
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, PR China.
authors.forename: Jing-long
authors.initials: JL
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, PR China. Electronic address: shenzhf@imm.ac.cn.
authors.forename: Zhu-fang
authors.initials: ZF
authors.lastname: Shen
mesh_terms: D000818:Animals; D001786:Blood Glucose; D004041:Dietary Fats; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011236:Prediabetic State / Q000517:prevention & control*; D016474:Weight-Bearing
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; C527173:jinqi jiantang
keywords: ACC; AMPK; AUC; Beta cell function; CON; ELSD; Evaporative Light Scattering Detector; GIR; GLUT2; Glucose transporter 2; HFD; HOMA-IR; Herbal effective fractions; High fat diet; Homeostasis Model Assessment ratio of insulin resistance; IFG; IGT; IOD; IR; ITT; Insulin resistance; JQ-R; MET; NOR; OGTT; Prediabetes; Refined-JinQi-JiangTang tablet; S.E.M; T2DM; TC; TG; Type 2 Diabetes Mellitus; acetyl CoA carboxylase; adenosine monophosphate-activated protein kinase; area under the curves; glucose infusion rate; group treated with metformin; high fat-diet; impaired fasting glucose; impaired glucose tolerance; insulin resistance; insulin tolerance test; integrated optical density; normal control; oral glucose tolerance test; standard error of mean; total cholesterol; total triglyceride; untreated control group