Isodihydrocapsiate stimulates plasma glucose uptake by activation of AMP-activated protein kinase

Biochemical and Biophysical Research Communications
Seung-Lark HwangTae-Lin Huh

Abstract

AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is implicated as a key factor in controlling whole body homeostasis, including fatty acid oxidation and glucose uptake. We report that a synthetic structural isomer of dihydrocapsiate, isodihydrocapsiate (8-methylnonanoic acid 3-hydroxy-4-methoxy benzyl ester) improves type 2 diabetes by activating AMPK through the LKB1 pathway. In L6 myotube cells, phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) and glucose uptake were significantly increased, whereas these effects were attenuated by an AMPK inhibitor, compound C. In addition, increased phosphorylation of AMPK and ACC by isodihydrocapsiate was significantly reduced by radicicol, an LKB1 destabilizer, suggesting that increased glucose uptake in L6 cells with isodihydrocapsiate treatment is predominantly accomplished by a LKB1-mediated AMPK activation pathway. Oral administration of isodihydrocapsiate to diabetic (db/db) mice reduced blood glucose levels by 40% after a 4-week treatment period. Our results support the development of isodihydrocapsiate as a potential therapeutic agent to target AMPK in type 2 diabetes.

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Citations

Feb 28, 2009·Acta Physiologica·G ZhouB B Zhang
May 27, 2014·Expert Opinion on Investigational Drugs·Jiun-Tsai LinYao-Jen Liang
Jan 28, 2012·Biochemical and Biophysical Research Communications·Seung-Lark HwangHyeun Wook Chang
Feb 19, 2011·Biochemical and Biophysical Research Communications·Ji-Hak JeongYoung-Chae Chang
Sep 29, 2011·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·A G Dulloo
Sep 20, 2015·European Journal of Pharmacology·Toshiro Matsui
Feb 7, 2012·Biochemical and Biophysical Research Communications·Na-Young HongDeok-Bae Park
May 13, 2010·Biochemical and Biophysical Research Communications·Seung-Lark HwangYoung-Chae Chang
Nov 11, 2008·Biochemical and Biophysical Research Communications·Seung-Lark HwangTae-Lin Huh
Jan 15, 2013·The Journal of Nutritional Biochemistry·Eun-Kyung YoonSeung-Lark Hwang
Feb 1, 2015·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Venkateswarlu KorthikuntaNarender Tadigoppula
Sep 7, 2018·Frontiers in Pharmacology·Aminu Mohammed, Md Shahidul Islam
Apr 28, 2018·Journal of Agricultural and Food Chemistry·Quancai SunDavid Julian McClements

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