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Title: Disruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity.
Authors: Yoshihara, Eiji
Fujimoto, Shimpei
Inagaki, Nobuya  kyouindb  KAKEN_id
Okawa, Katsuya
Masaki, So
Yodoi, Junji
Masutani, Hiroshi  kyouindb  KAKEN_id
Author's alias: 増谷, 弘
Keywords: Biological Sciences
Cell biology
Medical research
Molecular biology
Issue Date: Nov-2010
Publisher: Nature Publishing Group
Journal title: Nature communications
Volume: 1
Thesis number: 127
Abstract: 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.
Rights: © 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(Published Version): 10.1038/ncomms1127
PubMed ID: 21119640
Appears in Collections:Journal Articles

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