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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.
Mol Pharmacol. 2013 Jul; 84(1):147-57.MP

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.

Authors+Show Affiliations

College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23658008

Citation

Jeong, Yong-Tae, et al. "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." Molecular Pharmacology, vol. 84, no. 1, 2013, pp. 147-57.
Jeong YT, Kim YD, Jung YM, et al. 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. Mol Pharmacol. 2013;84(1):147-57.
Jeong, Y. T., Kim, Y. D., Jung, Y. M., Park, D. C., Lee, D. S., Ku, S. K., Li, X., Lu, Y., Chao, G. H., Kim, K. J., Lee, J. Y., Baek, M. C., Kang, W., Hwang, S. L., & Chang, H. W. (2013). 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. Molecular Pharmacology, 84(1), 147-57. https://doi.org/10.1124/mol.113.085100
Jeong YT, et al. 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. Mol Pharmacol. 2013;84(1):147-57. PubMed PMID: 23658008.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Jeong,Yong-Tae, AU - Kim,Yong Deuk, AU - Jung,Young-Mi, AU - Park,Dong-Chan, AU - Lee,Dong-Sub, AU - Ku,Sae-Kwang, AU - Li,Xian, AU - Lu,Yue, AU - Chao,Guang Hsuan, AU - Kim,Keuk-Jun, AU - Lee,Jai-Youl, AU - Baek,Moon-Chang, AU - Kang,Wonku, AU - Hwang,Seung-Lark, AU - Chang,Hyeun Wook, Y1 - 2013/05/08/ PY - 2013/5/10/entrez PY - 2013/5/10/pubmed PY - 2013/9/12/medline SP - 147 EP - 57 JF - Molecular pharmacology JO - Mol. Pharmacol. VL - 84 IS - 1 N2 - 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. SN - 1521-0111 UR - https://www.unboundmedicine.com/medline/citation/23658008/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_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=23658008 DB - PRIME DP - Unbound Medicine ER -