Low Molecular Weight Fucoidan Improves Endoplasmic Reticulum Stress-Reduced Insulin Sensitivity through AMP-Activated Protein Kinase Activation in L6 Myotubes and Restores Lipid Homeostasis in a Mouse Model of Type 2 Diabetes

Title
Low Molecular Weight Fucoidan Improves Endoplasmic Reticulum Stress-Reduced Insulin Sensitivity through AMP-Activated Protein Kinase Activation in L6 Myotubes and Restores Lipid Homeostasis in a Mouse Model of Type 2 Diabetes
Author(s)
장현욱정용태김용득정영미[정영미]이동섭[이동섭]구세광[구세광]이선유예조광선김극준[김극준]이재열[이재열]백문창[백문창]강원구황승락
Keywords
FATTY-ACID OXIDATION; DIET-INDUCED OBESITY; GLUCOSE-UPTAKE; CELLULAR-ENERGY; SKELETAL-MUSCLE; LIVER FIBROSIS; DB/DB MICE; IN-VIVO; METFORMIN; METABOLISM
Issue Date
201307
Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
Citation
MOLECULAR PHARMACOLOGY, v.84, no.1, pp.147 - 157
Abstract
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 obese diabetic mice (leptin receptor-deficient 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 low-density lipoprotein levels, and gradually reduced body weights by reducing lipid parameters. Furthermore, it effectively ameliorated glucose homeostasis by elevating glucose tolerance. In addition, the phosphorylation levels 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 the mammalian target of rapamycin-p70S61 kinase 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.
URI
http://hdl.handle.net/YU.REPOSITORY/29484http://dx.doi.org/10.1124/mol.113.085100
ISSN
0026-895X
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약학대학 > 약학부 > Articles
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