Vaccarin ameliorates insulin resistance and steatosis by activating the AMPK signaling pathway

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...

Full description

Saved in:
Bibliographic Details
Published in:European journal of pharmacology 2019-05, Vol.851, p.13-24
Main Authors: Lei, Yueyue, Gong, Leilei, Tan, Fanggen, Liu, Yixiao, Li, Shuangshuang, Shen, Houwang, Zhu, Min, Cai, Weiwei, Xu, Fei, Hou, Bao, Zhou, Yuetao, Han, Hongxiu, Qiu, Liying, Sun, Haijian
Format: Article
Language:English
Subjects:
AMPK
Insulin resistance
Steatosis
T2DM
vaccarin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2019.02.029