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

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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 invivois far less well understood. In Vnutknockout (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 β-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 cellsin vivoand suggest that vesicular ATP and/or its degradation products act as feedback regulators in catecholamine and insulin secretion, thereby regulating blood glucose homeostasis.

Original languageEnglish
Article number6689
JournalScientific reports
Volume4
DOIs
Publication statusPublished - Oct 21 2014

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Insulin Resistance
Adenosine Triphosphate
Glucose
Chromaffin Granules
Nucleotides
Insulin
Blood Glucose
Neuroendocrine Cells
Secretory Vesicles
Islets of Langerhans
Catecholamines
Fasting
Homeostasis
Hormones

All Science Journal Classification (ASJC) codes

  • General

Cite this

Sakamoto, S., Miyaji, T., Hiasa, M., Ichikawa, R., Uematsu, A., Iwatsuki, K., ... Moriyama, Y. (2014). Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity. Scientific reports, 4, [6689]. https://doi.org/10.1038/srep06689

Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity. / Sakamoto, Shohei; Miyaji, Takaaki; Hiasa, Miki; Ichikawa, Reiko; Uematsu, Akira; Iwatsuki, Ken; Shibata, Atsushi; Uneyama, Hisayuki; Takayanagi, Ryoichi; Yamamoto, Akitsugu; Omote, Hiroshi; Nomura, Masatoshi; Moriyama, Yoshinori.

In: Scientific reports, Vol. 4, 6689, 21.10.2014.

Research output: Contribution to journalArticle

Sakamoto, S, Miyaji, T, Hiasa, M, Ichikawa, R, Uematsu, A, Iwatsuki, K, Shibata, A, Uneyama, H, Takayanagi, R, Yamamoto, A, Omote, H, Nomura, M & Moriyama, Y 2014, 'Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity', Scientific reports, vol. 4, 6689. https://doi.org/10.1038/srep06689
Sakamoto, Shohei ; Miyaji, Takaaki ; Hiasa, Miki ; Ichikawa, Reiko ; Uematsu, Akira ; Iwatsuki, Ken ; Shibata, Atsushi ; Uneyama, Hisayuki ; Takayanagi, Ryoichi ; Yamamoto, Akitsugu ; Omote, Hiroshi ; Nomura, Masatoshi ; Moriyama, Yoshinori. / Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity. In: Scientific reports. 2014 ; Vol. 4.
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