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タイトル: | Disruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity. |
著者: | Yoshihara, Eiji Fujimoto, Shimpei Inagaki, Nobuya Okawa, Katsuya Masaki, So Yodoi, Junji Masutani, Hiroshi |
著者名の別形: | 増谷, 弘 |
キーワード: | Biological Sciences Cell biology Medical research Molecular biology |
発行日: | Nov-2010 |
出版者: | Nature Publishing Group |
誌名: | Nature communications |
巻: | 1 |
論文番号: | 127 |
抄録: | Type 2 diabetes mellitus (T2DM) is characterized by defects in both insulin sensitivity and glucose-stimulated insulin secretion (GSIS) and is often accompanied by obesity. In this study, we show that disruption of thioredoxin binding protein-2 (TBP-2, also called Txnip) in obese mice (ob/ob) dramatically improves hyperglycaemia and glucose intolerance, without affecting obesity or adipocytokine concentrations. TBP-2-deficient ob/ob mice exhibited enhanced insulin sensitivity with activated insulin receptor substrate-1/Akt signalling in skeletal muscle and GSIS in islets compared with ob/ob mice. The elevation of uncoupling protein-2 (UCP-2) expression in ob/ob islets was downregulated by TBP-2 deficiency. TBP-2 overexpression suppressed glucose-induced adenosine triphosphate production, Ca(2+) influx and GSIS. In β-cells, TBP-2 enhanced the expression level and transcriptional activity of UCP-2 by recruitment of peroxisome proliferator-activated receptor-γ co-activator-1α to the UCP-2 promoter. Thus, TBP-2 is a key regulatory molecule of both insulin sensitivity and GSIS in diabetes, raising the possibility that inhibition of TBP-2 may be a novel therapeutic approach for T2DM. |
著作権等: | © 2010 Macmillan Publishers Limited. This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
URI: | http://hdl.handle.net/2433/157353 |
DOI(出版社版): | 10.1038/ncomms1127 |
PubMed ID: | 21119640 |
出現コレクション: | 学術雑誌掲載論文等 |
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