PMID- 27742409 OWN - NLM STAT- MEDLINE DCOM- 20170321 LR - 20171116 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 193 DP - 2016 Dec 4 TI - Entada phaseoloides extract suppresses hepatic gluconeogenesis via activation of the AMPK signaling pathway. PG - 691-699 LID - S0378-8741(16)31274-0 [pii] LID - 10.1016/j.jep.2016.10.039 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: 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). MATERIALS AND 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 3beta (GSK3beta), respectively. Furthermore, TSEP reduced lipid accumulation and improved insulin sensitivity in hepatocytes. CONCLUSION: These findings provide evidence that TSEP exerts an antidiabetic effect by suppressing hepatic gluconeogenesis via the AMPK signaling pathway. CI - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Zheng, Tao AU - Zheng T AD - 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. FAU - Hao, Xincai AU - Hao X AD - College of Pharmacy, Hubei University of Medicine, Shiyan, Hubei, China. FAU - Wang, Qibin AU - Wang Q AD - Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China. FAU - Chen, Li AU - Chen L AD - Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China. FAU - Jin, Si AU - Jin S AD - 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. FAU - Bian, Fang AU - Bian F AD - 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. LA - eng PT - Journal Article DEP - 20161011 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Drugs, Chinese Herbal) RN - 0 (Hypoglycemic Agents) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/*metabolism MH - Animals MH - Cell Survival/drug effects MH - Dose-Response Relationship, Drug MH - Drugs, Chinese Herbal/isolation & purification/*pharmacology/therapeutic use MH - Fabaceae/*chemistry MH - Gluconeogenesis/*drug effects MH - Hep G2 Cells MH - Hepatocytes/*drug effects/enzymology/metabolism MH - Humans MH - Hypoglycemic Agents/isolation & purification/*pharmacology/therapeutic use MH - Lipid Metabolism/drug effects MH - Mice MH - Primary Cell Culture MH - Seeds/chemistry MH - Signal Transduction OTO - NOTNLM OT - AMP-activated protein kinase OT - Entada phaseoloides (L.) Merr. OT - Gluconeogenesis OT - Saponins OT - Type 2 Diabetes mellitus EDAT- 2016/10/16 06:00 MHDA- 2017/03/23 06:00 CRDT- 2016/10/16 06:00 PHST- 2016/05/27 00:00 [received] PHST- 2016/10/09 00:00 [revised] PHST- 2016/10/10 00:00 [accepted] PHST- 2016/10/16 06:00 [pubmed] PHST- 2017/03/23 06:00 [medline] PHST- 2016/10/16 06:00 [entrez] AID - S0378-8741(16)31274-0 [pii] AID - 10.1016/j.jep.2016.10.039 [doi] PST - ppublish SO - J Ethnopharmacol. 2016 Dec 4;193:691-699. doi: 10.1016/j.jep.2016.10.039. Epub 2016 Oct 11.