title: Entada phaseoloides extract suppresses hepatic gluconeogenesis via activation of the AMPK signaling pathway.
abstract: BACKGROUND
  The seed of Entada phaseoloides (L.) Merr. (Entada phaseoloides) has been long used as a folk medicine for the treatment of Diabetes mellitus by Chinese ethnic minorities. Recent reports have demonstrated that total saponins from Entada phaseoloides (TSEP) could reduce fasting blood glucose in type 2 diabetic rats. However, the mechanism has not been fully elucidated. The aim of this study was to explore the underlying mechanisms of TSEP on type 2 Diabetes mellitus (T2DM).
  
  
  METHODS
  Primary mouse hepatocytes and HepG2 cells were used to investigate the effects of TSEP on gluconeogenesis. After treatment with TSEP, glucose production, genes expression levels of Glucose-6-phosphatase (G6pase) and Phosphoenoylpyruvate carboxykinase (Pepck) were detected. The efficacy and underlying mechanism of TSEP on AMP-activated protein kinase (AMPK) signaling pathway were determinated.
  
  
  RESULTS
  TSEP significantly inhibited glucose production and the gluconeogenic gene expression. Treatment with TSEP elevated the phosphorylation of AMPK, which in turn promoted the phosphorylation of acetyl coenzyme A (ACC) and Akt/glycogen synthase kinase 3β (GSK3β), respectively. Furthermore, TSEP reduced lipid accumulation and improved insulin sensitivity in hepatocytes.
  
  
  CONCLUSIONS
  These findings provide evidence that TSEP exerts an antidiabetic effect by suppressing hepatic gluconeogenesis via the AMPK signaling pathway.
authors.affiliation: Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China; Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zheng
authors.affiliation: College of Pharmacy, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Xincai
authors.initials: X
authors.lastname: Hao
authors.affiliation: Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: jinsi@hust.edu.cn.
authors.forename: Si
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; The Affiliated Hospital of Xiangyang Central Hospital of Hubei College of Arts and Sciences, Xiangyang, China. Electronic address: bianfang45@sina.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Bian
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D007887:Fabaceae / Q000737:chemistry*; D005943:Gluconeogenesis / Q000187:drug effects*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D061251:Primary Cell Culture; D012639:Seeds / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; Entada phaseoloides (L.) Merr.; Gluconeogenesis; Saponins; Type 2 Diabetes mellitus