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Tanshinone IIA improves endoplasmic reticulum stress-induced insulin resistance through AMP-activated protein kinase.

Abstract
The aim of the present study was to determine the effect of Tanshinone IIA (Tan IIA) on endoplasmic reticulum (ER) stress-induced insulin resistance in L6 myotubes and db/db mice. ER stress markers, RNA-activated protein kinase-like ER resident kinase (PERK), JNK, and AMPK activity were determined in tunicamycin-treated L6 myotubes. Insulin resistance was monitored using glucose uptake assays in vitro and blood glucose levels in vivo. Tan IIA clearly suppressed the phosphorylations of PERK and JNK and potentiated insulin-mediated Akt phosphorylation as well as glucose uptake via AMPK activation under ER stress. Furthermore, these effects are completely abrogated by siRNA-mediated knockdown of AMPK or LKB1. In addition, Tan IIA reduced blood glucose levels and body weights in db/db mice without altering food intake. These findings suggest that Tan IIA enhances insulin sensitivity and improves glucose metabolic disorders by increasing AMPK activity and attenuating ER stress-induced insulin resistance.
AuthorsSeung-Lark Hwang, Ju Hye Yang, Yong-Tae Jeong, Yong Deuk Kim, Xian Li, Yue Lu, Young-Chae Chang, Kun Ho Son, Hyeun Wook Chang
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 430 Issue 4 Pg. 1246-52 (Jan 25 2013) ISSN: 1090-2104 [Electronic] United States
PMID23266607 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Inc. All rights reserved.
Chemical References
  • Abietanes
  • Drugs, Chinese Herbal
  • Hypoglycemic Agents
  • tanshinone
  • Tunicamycin
  • AMP-Activated Protein Kinases
Topics
  • AMP-Activated Protein Kinases (metabolism)
  • Abietanes (pharmacology)
  • Animals
  • Cell Line
  • Drugs, Chinese Herbal (pharmacology)
  • Endoplasmic Reticulum Stress (drug effects)
  • Hypoglycemic Agents (pharmacology)
  • Insulin Resistance
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Fibers, Skeletal (drug effects, enzymology)
  • Tunicamycin (pharmacology)

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