title: 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.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Seung-Lark
authors.initials: SL
authors.lastname: Hwang
authors.forename: Ju Hye
authors.initials: JH
authors.lastname: Yang
authors.forename: Yong-Tae
authors.initials: YT
authors.lastname: Jeong
authors.forename: Yong Deuk
authors.initials: YD
authors.lastname: Kim
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.forename: Kun Ho
authors.initials: KH
authors.lastname: Son
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D045784:Abietanes; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; C021751:tanshinone; D014415:Tunicamycin; D055372:AMP-Activated Protein Kinases