論文

査読有り 筆頭著者
2014年10月

Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity

SCIENTIFIC REPORTS
  • Shohei Sakamoto
  • Takaaki Miyaji
  • Miki Hiasa
  • Reiko Ichikawa
  • Akira Uematsu
  • Ken Iwatsuki
  • Atsushi Shibata
  • Hisayuki Uneyama
  • Ryoichi Takayanagi
  • Akitsugu Yamamoto
  • Hiroshi Omote
  • Masatoshi Nomura
  • Yoshinori Moriyama
  • 全て表示

4
開始ページ
6689
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/srep06689
出版者・発行元
NATURE PUBLISHING GROUP

Neuroendocrine cells store ATP in secretory granules and release it along with hormones that may trigger a variety of cellular responses in a process called purinergic chemical transmission. Although the vesicular nucleotide transporter (VNUT) has been shown to be involved in vesicular storage and release of ATP, its physiological relevance in vivo is far less well understood. In Vnut knockout (Vnut(-/-)) mice, we found that the loss of functional VNUT in adrenal chromaffin granules and insulin granules in the islets of Langerhans led to several significant effects. Vesicular ATP accumulation and depolarization-dependent ATP release were absent in the chromaffin granules of Vnut(-/-) mice. Glucose-responsive ATP release was also absent in pancreatic beta-cells in Vnut(-/-) mice, while glucose-responsive insulin secretion was enhanced to a greater extent than that in wild-type tissue. Vnut(-/-) mice exhibited improved glucose tolerance and low blood glucose upon fasting due to increased insulin sensitivity. These results demonstrated an essential role of VNUT in vesicular storage and release of ATP in neuroendocrine cells in vivo and suggest that vesicular ATP and/or its degradation products act as feedback regulators in catecholamine and insulin secretion, thereby regulating blood glucose homeostasis.

リンク情報
DOI
https://doi.org/10.1038/srep06689
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25331291
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000343591100001&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/srep06689
  • ISSN : 2045-2322
  • PubMed ID : 25331291
  • Web of Science ID : WOS:000343591100001

エクスポート
BibTeX RIS