Ascofuranone prevents ER stress-induced insulin resistance via activation of AMP-activated protein kinase in L6 myotube cells

Title
Ascofuranone prevents ER stress-induced insulin resistance via activation of AMP-activated protein kinase in L6 myotube cells
Author(s)
장현욱황승락이인규[이인규]양병근[양병근]Junji Magae[Junji Magae]Young-Chae Chang[Young-Chae Chang]
Keywords
SKELETAL-MUSCLE; GLUCOSE-TRANSPORT; SYSTEM; ENERGY; ASCOCHLORIN; ANTITUMOR; METFORMIN; CASCADE; TRANSLOCATION; ANTIBIOTICS
Issue Date
201006
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.396, no.4, pp.967 - 972
Abstract
The current study presents that ascofuranone isolated from a phytopathogenic fungus. Ascochyta viciae, has antitumor activity against various transplantable tumors and a considerable hypolipidemic activity. AMP-activated protein kinase (AMPK) plays a critical role in cellular glucose and lipid homeostasis. We found that ascofuranone improves ER stress-induced insulin resistance by activating AMPK through the LKB1 pathway. In L6 myotube cells, ascofuranone treatment increased the phosphorylation of the Thr-172 residue of the AMPK alpha subunit and the Ser-79 subunit of acetyl-CoA carboxylase (ACC) and cellular glucose uptake. Ascofuranone-induced phosphorylation of AMPK and ACC was not increased in A549 cells lacking LKB1. Interestingly, ascofuranone treatment also improved insulin signaling impaired by ER stress in L6 myotube cells. These effects were all reversed by pretreatment with Compound C, an AMPK inhibitor or with adenoviral-mediated dominant-negative AMPK alpha 2. Taken together, these results indicated that ascofuranone-mediated enhancement of glucose uptake and reduction of impaired insulin sensitivity in L6 cells is predominantly accomplished by activating AMPK, thereby mediating beneficial effects in type 2 diabetes and insulin resistance. (C) 2010 Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/22379http://dx.doi.org/10.1016/j.bbrc.2010.05.034
ISSN
0006-291X
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약학대학 > 약학부 > Articles
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