Pinusolide improves high glucose-induced insulin resistance via activation of AMP-activated protein kinase

Title
Pinusolide improves high glucose-induced insulin resistance via activation of AMP-activated protein kinase
Author(s)
장현욱황승락정용태양주혜이선유예손종근
Keywords
SKELETAL-MUSCLE; BIOTA-ORIENTALIS; FACTOR ANTAGONIST; METFORMIN; ENERGY; SENSITIVITY; CELLS; LKB1; TRANSLOCATION; CONTRACTION
Issue Date
201308
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.437, no.3, pp.374 - 379
Abstract
Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in the maintenance of cellular energy homeostasis, and several natural compounds that activate AMPK possibly enhance glucose uptake by muscle cells. In this study, we found that pinusolide stimulated AMPK phosphorylation and glucose uptake and these effects were significantly reduced by siRNA LKB1 or compound C, suggesting that enhanced glucose uptake by pinusolide is predominantly accomplished via an LKB1-mediated AMPK activation pathway. An insulin resistance state was induced by exposing cells to 30 mM glucose, as indicated by reduced insulin-stimulated tyrosine phosphorylation of IRS-1 and glucose uptake. Under these conditions, the phosphorylation of AMPK and ACC were decreased. Surprisingly, disrupted insulin signaling and decreased AMPK activity by high glucose concentrations were prevented by pinusolide. Moreover, this treatment increased insulin-stimulated glucose uptake via AMPK activation. Taken together, our findings suggest a link between high glucose and insulin resistance in muscle cells, and provide further evidence that pinusolide attenuates blockade of insulin signaling by enhancing IRS-1 tyrosine phosphorylation by the activating the AMPK pathway. In addition, this study indicates the targeting of AMPK represents a new therapeutic strategy for hyperglycemia-induced insulin resistance and type 2 diabetes. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/29230http://dx.doi.org/10.1016/j.bbrc.2013.06.084
ISSN
0006-291X
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약학대학 > 약학부 > Articles
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