PMID- 30779918
OWN - NLM
STAT- MEDLINE
DCOM- 20190722
LR  - 20211204
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 851
DP  - 2019 May 15
TI  - Vaccarin ameliorates insulin resistance and steatosis by activating the AMPK 
      signaling pathway.
PG  - 13-24
LID - S0014-2999(19)30128-1 [pii]
LID - 10.1016/j.ejphar.2019.02.029 [doi]
AB  - Destructive glucose and lipid metabolism in the liver is a crucial characteristic 
      of type 2 diabetes mellitus (T2DM), eventually leading to insulin resistance and 
      subsequent hyperglycemia and hyperlipidemia. Vaccarin is an active flavonoid 
      glycoside associated with various biological functions, but its effects on 
      glucose and lipid metabolic disorder in T2DM are still unclear. In this study, 
      glucosamine (GlcN) and free fatty acids (FFAs, oleate/palmitate, 2:1 ratio) were 
      applied to mimic insulin resistance and lipid deposition in HepG2 cells, 
      respectively. Type 2 diabetic mice were induced using a high-fat diet (HFD) 
      together with streptozotocin (STZ). GlcN stimulation was found to upregulate 
      glucose production and gluconeogenesis but downregulate glycogen synthesis and 
      phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase 
      (AMPK) in HepG2 cells, abnormal changes that were reversed by vaccarin. 
      Furthermore, lipid accumulation was enhanced, but AMPK was inactivated in 
      FFAs-exposed HepG2 cells, issues that were rectified by vaccarin treatment. These 
      ameliorative effects of vaccarin on insulin resistance and steatosis were 
      eliminated by AMPK inhibitor Compound C. In type 2 diabetic mice, chronic 
      vaccarin administration decreased fasting blood glucose and lipid levels in both 
      serum and the liver, and improved insulin sensitivity and steatosis in the liver. 
      Taken together, these results suggest that vaccarin attenuates insulin resistance 
      and steatosis by activating the AMPK signaling pathway.
CI  - Copyright (c) 2019. Published by Elsevier B.V.
FAU - Lei, Yueyue
AU  - Lei Y
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Gong, Leilei
AU  - Gong L
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Tan, Fanggen
AU  - Tan F
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Liu, Yixiao
AU  - Liu Y
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Li, Shuangshuang
AU  - Li S
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Shen, Houwang
AU  - Shen H
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Zhu, Min
AU  - Zhu M
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Cai, Weiwei
AU  - Cai W
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Xu, Fei
AU  - Xu F
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Hou, Bao
AU  - Hou B
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Zhou, Yuetao
AU  - Zhou Y
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China.
FAU - Han, Hongxiu
AU  - Han H
AD  - Wuxi Hongqiao Hospital, Wuxi, Jiangsu 214122, PR China.
FAU - Qiu, Liying
AU  - Qiu L
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu 214122, PR China. Electronic address: qiulydoc@sina.com.
FAU - Sun, Haijian
AU  - Sun H
AD  - Department of Pharmacology, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore 117597, Singapore. Electronic address: 
      phcsunh@nus.edu.sg.
LA  - eng
PT  - Journal Article
DEP - 20190216
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Flavonoids)
RN  - 0 (Glycosides)
RN  - 0 (vaccarin H)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (STK11 protein, human)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Enzyme Activation/drug effects
MH  - Fatty Acids, Nonesterified/pharmacology
MH  - Fatty Liver/*drug therapy/metabolism/pathology
MH  - Flavonoids/*pharmacology/therapeutic use
MH  - Glucose/metabolism
MH  - Glycosides/*pharmacology/therapeutic use
MH  - Hep G2 Cells
MH  - Humans
MH  - *Insulin Resistance
MH  - Liver/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Protein Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - AMPK
OT  - Insulin resistance
OT  - Steatosis
OT  - T2DM
OT  - vaccarin
EDAT- 2019/02/20 06:00
MHDA- 2019/07/23 06:00
CRDT- 2019/02/20 06:00
PHST- 2019/01/25 00:00 [received]
PHST- 2019/02/14 00:00 [revised]
PHST- 2019/02/15 00:00 [accepted]
PHST- 2019/02/20 06:00 [pubmed]
PHST- 2019/07/23 06:00 [medline]
PHST- 2019/02/20 06:00 [entrez]
AID - S0014-2999(19)30128-1 [pii]
AID - 10.1016/j.ejphar.2019.02.029 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2019 May 15;851:13-24. doi: 10.1016/j.ejphar.2019.02.029. Epub 
      2019 Feb 16.