PMID- 30524480 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1741-427X (Print) IS - 1741-4288 (Electronic) IS - 1741-427X (Linking) VI - 2018 DP - 2018 TI - Dandelion Chloroform Extract Promotes Glucose Uptake via the AMPK/GLUT4 Pathway in L6 Cells. PG - 1709587 LID - 10.1155/2018/1709587 [doi] LID - 1709587 AB - The number of patients with type 2 diabetes mellitus (T2DM) is increasing rapidly worldwide. Glucose transporter 4 (GLUT4) is one of the main proteins that transport blood glucose into the cells and is a target in the treatment of T2DM. In this study, we investigated the mechanism of action of dandelion chloroform extract (DCE) on glucose uptake in L6 cells. The glucose consumption of L6 cell culture supernatant was measured by a glucose uptake assay kit, and the dynamic changes of intracellular GLUT4 and calcium (Ca(2+)) levels were monitored by laser scanning confocal microscopy in L6 cell lines stably expressing IRAP-mOrange. The GLUT4 fusion with the plasma membrane (PM) was traced via myc-GLUT4-mOrange. GLUT4 expression and AMP-activated protein kinase (AMPK), protein kinase B (PKB/Akt), protein kinase C (PKC), and phosphorylation levels were determined by performing western blotting. GLUT4 mRNA expression was detected by real-time PCR. DCE up-regulated GLUT4 expression, promoted GLUT4 translocation and fusion to the membrane eventually leading to glucose uptake, and induced AMPK phosphorylation in L6 cells. The AMPK inhibitory compound C significantly inhibited DCE-induced GLUT4 expression and translocation while no inhibitory effect was observed by the phosphatidylinositol 3-kinase (PI3K) inhibitor Wortmannin and PKC inhibitor Go6983. These data suggested that DCE promoted GLUT4 expression and transport to the membrane through the AMPK signaling pathway, thereby stimulating GLUT4 fusion with PM to enhance glucose uptake in L6 cells. DCE-induced GLUT4 translocation was also found to be Ca(2+)-independent. Together, these findings indicate that DCE could be a new hypoglycemic agent for the treatment of T2DM. FAU - Zhao, Ping AU - Zhao P AUID- ORCID: 0000-0002-5348-6126 AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in the Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China. AD - National Demonstration Center for Experimental Ethnopharmacology Education, South-Central University for Nationalities, Wuhan 430074, China. FAU - Ming, Qian AU - Ming Q AUID- ORCID: 0000-0003-0389-3396 AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in the Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China. FAU - Xiong, Mingrui AU - Xiong M AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in the Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China. FAU - Song, Guanjun AU - Song G AUID- ORCID: 0000-0002-8300-6330 AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in the Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China. FAU - Tan, Li AU - Tan L AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in the Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China. FAU - Tian, Di AU - Tian D AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in the Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China. FAU - Liu, Jia AU - Liu J AUID- ORCID: 0000-0003-2474-8374 AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in the Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China. FAU - Huang, Zhao AU - Huang Z AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in the Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China. FAU - Ma, Jingyi AU - Ma J AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in the Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China. FAU - Shen, Jinhua AU - Shen J AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in the Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China. FAU - Liu, Qing-Hua AU - Liu QH AUID- ORCID: 0000-0003-3914-0775 AD - Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in the Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China. FAU - Yang, Xinzhou AU - Yang X AUID- ORCID: 0000-0003-1697-2923 AD - National Demonstration Center for Experimental Ethnopharmacology Education, South-Central University for Nationalities, Wuhan 430074, China. AD - School of Pharmaceutical Sciences, South-Central University for Nationalities, 182 Min-Zu Road, Wuhan 430074, China. LA - eng PT - Journal Article DEP - 20181107 PL - United States TA - Evid Based Complement Alternat Med JT - Evidence-based complementary and alternative medicine : eCAM JID - 101215021 PMC - PMC6247471 EDAT- 2018/12/14 06:00 MHDA- 2018/12/14 06:01 PMCR- 2018/11/07 CRDT- 2018/12/08 06:00 PHST- 2018/04/23 00:00 [received] PHST- 2018/08/02 00:00 [revised] PHST- 2018/09/04 00:00 [accepted] PHST- 2018/12/08 06:00 [entrez] PHST- 2018/12/14 06:00 [pubmed] PHST- 2018/12/14 06:01 [medline] PHST- 2018/11/07 00:00 [pmc-release] AID - 10.1155/2018/1709587 [doi] PST - epublish SO - Evid Based Complement Alternat Med. 2018 Nov 7;2018:1709587. doi: 10.1155/2018/1709587. eCollection 2018.