RT Journal Article SR Electronic T1 Low Molecular Weight Fucoidan (LMWF) Improves ER Stress-Reduced Insulin Sensitivity through AMPK Activation in L6 Myotubes and Restores Lipid Homeostasis in a Mouse Model of Type 2 Diabetes JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP mol.113.085100 DO 10.1124/mol.113.085100 A1 Yong-Tae Jeong A1 Yong Deuk Kim A1 Young-Mi Jung A1 Dong-Chan Park A1 Dong-Sub Lee A1 Sae-Kwang Ku A1 Xian Li A1 Yue Lu A1 Guang Hsuan Chao A1 Keuk-Jun Kim A1 Jai-Youl Lee A1 Moon-Chang Baek A1 Wonku Kang A1 Seung-Lark Hwang A1 Hyeun Wook Chang YR 2013 UL http://molpharm.aspetjournals.org/content/early/2013/05/08/mol.113.085100.abstract AB Low molecular weight fucoidan (LMWF) is widely used to treat metabolic disorders, but its physiologic effects have not been well determined. In the present study, we investigated the metabolic effects of LMWF in db/db mice and the underlying molecular mechanisms involved in endoplasmic reticulum (ER) stress-responsive L6 myotubes. The effect of LMWF-mediated AMP-activated protein kinase (AMPK) activation on insulin resistance via regulation of the ER stress-dependent pathway was examined in vitro and in vivo. In db/db mice, LMWF markedly reduced serum glucose, triglyceride, cholesterol, and LDL levels, and gradually reduced body weights by reducing lipid parameters. Furthermore, it effectively ameliorated glucose homeostasis by elevating glucose tolerance. In addition, the phosphorylation level of AMPK and Akt were markedly reduced by ER stressor, and subsequently, glucose uptake and fatty acid oxidation were also reduced. However, these adverse effects of ER stress were significantly ameliorated by LMWF. Finally, in L6 myotubes, LMWF markedly reduced the ER stress-induced upregulation of mammalian target of rapamycin (mTOR)-p70S61 kinase (S6K) network and subsequently improved the action of insulin via AMPK stimulation. Our findings suggest that AMPK activation by LMWF could prevent metabolic diseases by controlling the ER stress-dependent pathway and that this beneficial effect of LMWF provides a potential therapeutic strategy for ameliorating ER stress-mediated metabolic dysfunctions.