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ID 49928
フルテキストURL
著者
Nakatsuka, Atsuko Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
Wada, Jun Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
Iseda, Izumi Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
Teshigawara, Sanae Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
Higashio, Kanji Metabolome Pharmaceut Inc
Murakami, Kazutoshi Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
Kanzaki, Motoko Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
Inoue, Kentaro Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
Terami, Takahiro Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
Katayama, Akihiro Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
Hida, Kazuyuki Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci, Okayama
Eguchi, Jun Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
Horiguchi, Chikage Sato Okayama Univ, Dept Diabet Nephropathy, Grad Sch Med Dent & Pharmaceut Sci
Ogawa, Daisuke Okayama Univ, Dept Diabet Nephropathy, Grad Sch Med Dent & Pharmaceut Sci
Matsuki, Yasushi Dainippon Sumitomo Pharma, Genom Sci Labs
Hiramatsu, Ryuji Dainippon Sumitomo Pharma, Genom Sci Labs
Yagita, Hideo Juntendo Univ, Sch Med, Dept Immunol
Kakuta, Shigeru Univ Tokyo, Inst Med Sci, Ctr Expt Med & Syst Biol
Iwakura, Yoichiro Univ Tokyo, Inst Med Sci, Ctr Expt Med & Syst Biol
Makino, Hirofumi Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
抄録
It is unknown whether adipokines derived from adipose tissues modulate endoplasmic reticulum (ER) stress induced in obesity. Here, we show that visceral adipose tissue-derived serine protease inhibitor (vaspin) binds to cell-surface 78-kDa glucose-regulated protein (GRP78), which is recruited from ER to plasma membrane under ER stress. Vaspin transgenic mice were protected from diet-induced obesity, glucose intolerance, and hepatic steatosis, while vaspin-deficient mice developed glucose intolerance associated with upregulation of ER stress markers. With tandem affinity tag purification using HepG2 cells, we identified GRP78 as an interacting molecule. The complex formation of vaspin, GRP78, and murine tumor cell DnaJ-like protein 1 (MTJ-1) (DnaJ homolog, subfamily C, member 1) on plasma membrane was confirmed by cell-surface labeling with biotin and immunoprecipitation in liver tissues and H-4-II-E-C3 cells. The addition of recombinant human vaspin in the cultured H-4-II-E-C3 cells also increased the phosphorylation of Akt and AMP-activated protein kinase (AMPK) in a dose-dependent manner, and anti-GRP78 antibodies completely abrogated the vaspin-induced upregulation of pAkt and pAMPK Vaspin is a novel ligand for cell-surface GRP78/MTJ-1 complex, and its subsequent signals exert beneficial effects on ER stress-induced metabolic dysfunctions. Diabetes 61:2823-2832, 2012
発行日
2012-11
出版物タイトル
Diabetes
61巻
11号
開始ページ
2823
終了ページ
2832
ISSN
0012-1797
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.2337/db12-0232
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/49735
言語
English
論文のバージョン
author
査読
有り
DOI
Web of Sience KeyUT