PMID- 31609623 OWN - NLM STAT- MEDLINE DCOM- 20191209 LR - 20191217 IS - 1520-5118 (Electronic) IS - 0021-8561 (Linking) VI - 67 IP - 47 DP - 2019 Nov 27 TI - Gymnemic Acid Ameliorates Hyperglycemia through PI3K/AKT- and AMPK-Mediated Signaling Pathways in Type 2 Diabetes Mellitus Rats. PG - 13051-13060 LID - 10.1021/acs.jafc.9b04931 [doi] AB - Gymnemic acid (GA) isolated from Gymnema sylvestre (Retz.) Schult. has been shown to have antihyperglycemic activity; however, the molecular mechanisms governing these effects are unclear. In this study, GA (40 and 80 mg kg(-1) day(-1)) was evaluated by type 2 diabetes mellitus (T2DM) rats to explore its hypoglycemic activity and underlying mechanisms of action. The results indicated that GA decreased fasting blood glucose (FBG) concentrations by 26.7% and lowered insulin concentrations by 16.1% after oral administration of GA at a dose of 80 mg kg(-1) day(-1) for 6 weeks in T2DM rats. Our data showed that real-time polymerase chain reaction and western blot indicated that GA upregulated the level of phosphatidylinositol-3-kinase (PI3K) and glycogen synthesis (GS) and promoted the phosphorylation of protein kinase B (Akt) while downregulated the expression of glycogen synthesis kinase-3beta (GSK-3beta) in T2DM rats. In addition, key proteins involved in adenosine monophosphate (AMP)-activated protein kinase (AMPK)-mediated gluconeogenesis [such as phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G6Pase)] were downregulated in GA-treated T2DM rats. In summary, the hypoglycemic mechanisms of GA may be related to promoting insulin signal transduction and activating PI3K/Akt- and AMPK-mediated signaling pathways in T2DM rats. FAU - Li, Yumeng AU - Li Y AD - Key Laboratory of Food Nutrition and Safety (Tianjin University of Science and Technology) , Ministry of Education , Tianjin 300457 , People's Republic of China. FAU - Liu, Yaping AU - Liu Y AD - Key Laboratory of Food Nutrition and Safety (Tianjin University of Science and Technology) , Ministry of Education , Tianjin 300457 , People's Republic of China. FAU - Liang, Junjie AU - Liang J AD - Key Laboratory of Food Nutrition and Safety (Tianjin University of Science and Technology) , Ministry of Education , Tianjin 300457 , People's Republic of China. FAU - Wang, Tianxin AU - Wang T AD - Key Laboratory of Food Nutrition and Safety (Tianjin University of Science and Technology) , Ministry of Education , Tianjin 300457 , People's Republic of China. FAU - Sun, Mingzhe AU - Sun M AD - Key Laboratory of Food Nutrition and Safety (Tianjin University of Science and Technology) , Ministry of Education , Tianjin 300457 , People's Republic of China. FAU - Zhang, Zesheng AU - Zhang Z AUID- ORCID: 0000-0002-0173-9355 AD - Key Laboratory of Food Nutrition and Safety (Tianjin University of Science and Technology) , Ministry of Education , Tianjin 300457 , People's Republic of China. AD - Tianjin Food Safety & Low Carbon Manufacturing Collaborative Innovation Center , Tianjin 300457 , People's Republic of China. LA - eng PT - Journal Article DEP - 20191118 PL - United States TA - J Agric Food Chem JT - Journal of agricultural and food chemistry JID - 0374755 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Saponins) RN - 0 (Triterpenes) RN - 327O38FRK1 (gymnemic acid) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/genetics/*metabolism MH - Animals MH - Diabetes Mellitus, Type 2/*drug therapy/enzymology/genetics MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Insulin/metabolism MH - Male MH - Phosphatidylinositol 3-Kinase/genetics/*metabolism MH - Proto-Oncogene Proteins c-akt/genetics/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Saponins/*administration & dosage MH - Signal Transduction/drug effects MH - Triterpenes/*administration & dosage OTO - NOTNLM OT - PI3K/Akt and AMPK signaling OT - diabetes mellitus OT - glucose metabolism OT - gymnemic acid OT - insulin resistance EDAT- 2019/10/15 06:00 MHDA- 2019/12/18 06:00 CRDT- 2019/10/15 06:00 PHST- 2019/10/15 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/10/15 06:00 [entrez] AID - 10.1021/acs.jafc.9b04931 [doi] PST - ppublish SO - J Agric Food Chem. 2019 Nov 27;67(47):13051-13060. doi: 10.1021/acs.jafc.9b04931. Epub 2019 Nov 18.