論文

査読有り
2014年2月

Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
  • Tomoyuki Yuasa
  • ,
  • Kikuko Amo
  • ,
  • Shuhei Ishikura
  • ,
  • Hisao Nagaya
  • ,
  • Keiji Uchiyama
  • ,
  • Seiichi Hashida
  • ,
  • Yousuke Ebina

445
1
開始ページ
236
終了ページ
243
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbrc.2014.01.187
出版者・発行元
ACADEMIC PRESS INC ELSEVIER SCIENCE

Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. IR has a pivotal role in glucose homeostasis and diabetes development; therefore, cleavage of IR promoted by hyperglycemia is involved in insulin resistance and glucose toxicity. To elucidate the physiology of sIR, we developed an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes. Among four human cell lines that expressed IR, spontaneous cleavage of IR occurred only in HepG2 cells. The molecular characteristics of sIR derived from HepG2 cells were similar to those of sIR detected in human plasma. The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. Additionally, glucose-dependent increment of sIR was reversible in this model. These results are consistent with the observation of plasma sIR in patients with diabetes. Using this model, O-linked N-acetylglucosamine modification was determined to be involved in high-glucose-induced IR cleavage. A calcium-dependent protease was shown to cleave IR extracellularly. These findings show that this in vitro model could be useful for determining the molecular mechanism underlying IR cleavage. (C) 2014 Elsevier Inc. All rights reserved.

Web of Science ® 被引用回数 : 9

リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2014.01.187
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/24508798
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000332749400041&DestApp=WOS_CPL

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