Secretory granule-mediated co-secretion of L-glutamate and glucagon triggers glutamatergic signal transmission in islets of Langerhans

Mitsuko Hayashi, Hiroshi Yamada, Shunsuke Uehara, Riyo Morimoto, Akiko Muroyama, Shouki Yatsushiro, Jun Takeda, Akitsugu Yamamoto, Yoshinori Moriyama

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Abstract

L-Glutamate is believed to function as an intercellular transmitter in the islets of Langerhans. However, critical issues, i.e. where, when and how L-glutamate appears, and what happens upon stimulation of glutamate receptors in the islets, remain unresolved. Vesicular glutamate transporter 2 (VGLUT2), an isoform of the vesicular glutamate transporter essential for neuronal storage of L-glutamate, is expressed in α cells (Hayashi, M., Otsuka, M., Morimoto, R., Hirota, S., Yatsushiro, S., Takeda, J., Yamamoto, A., and Moriyama, Y. (2001) J. Biol. Chem. 276, 43400-43406). Here we show that VGLUT2 is specifically localized in glucagon-containing secretory granules but not in synaptic-like microvesicles in αTC6 cells, clonal α cells, and islet α cells. VGLUT1, another VGLUT isoform, is also expressed and localized in secretory granules in α cells. Low glucose conditions triggered co-secretion of stoichiometric amounts of L-glutamate and glucagon from αTC6 cells and isolated islets, which is dependent on temperature and Ca2+ and inhibited by phentolamine. Similar cosecretion of L-glutamate and glucagon from islets was observed upon stimulation of β-adrenergic receptors with isoproterenol. Under low glucose conditions, stimulation of glutamate receptors facilitates secretion of γ-aminobutyric acid from MIN6 m9, clonal β cells, and isolated islets. These results indicate that co-secretion of L-glutamate and glucagon from α cells under low glucose conditions triggers GABA secretion from α cells and defines the mode of action of L-glutamate as a regulatory molecule for the endocrine function. To our knowledge, this is the first example of secretory granule-mediated glutamatergic signal transmission.

Original languageEnglish
Pages (from-to)1966-1974
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number3
DOIs
Publication statusPublished - Jan 17 2003

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Secretory Vesicles
Glucagon
Islets of Langerhans
Glutamic Acid
Vesicular Glutamate Transport Protein 2
Glutamate Receptors
Glucose
Protein Isoforms
Vesicular Glutamate Transport Proteins
Aminobutyrates
Phentolamine
Isoproterenol
gamma-Aminobutyric Acid
Adrenergic Receptors
Transmitters
Molecules
Temperature

ASJC Scopus subject areas

  • Biochemistry

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Secretory granule-mediated co-secretion of L-glutamate and glucagon triggers glutamatergic signal transmission in islets of Langerhans. / Hayashi, Mitsuko; Yamada, Hiroshi; Uehara, Shunsuke; Morimoto, Riyo; Muroyama, Akiko; Yatsushiro, Shouki; Takeda, Jun; Yamamoto, Akitsugu; Moriyama, Yoshinori.

In: Journal of Biological Chemistry, Vol. 278, No. 3, 17.01.2003, p. 1966-1974.

Research output: Contribution to journalArticle

Hayashi, M, Yamada, H, Uehara, S, Morimoto, R, Muroyama, A, Yatsushiro, S, Takeda, J, Yamamoto, A & Moriyama, Y 2003, 'Secretory granule-mediated co-secretion of L-glutamate and glucagon triggers glutamatergic signal transmission in islets of Langerhans', Journal of Biological Chemistry, vol. 278, no. 3, pp. 1966-1974. https://doi.org/10.1074/jbc.M206758200
Hayashi, Mitsuko ; Yamada, Hiroshi ; Uehara, Shunsuke ; Morimoto, Riyo ; Muroyama, Akiko ; Yatsushiro, Shouki ; Takeda, Jun ; Yamamoto, Akitsugu ; Moriyama, Yoshinori. / Secretory granule-mediated co-secretion of L-glutamate and glucagon triggers glutamatergic signal transmission in islets of Langerhans. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 3. pp. 1966-1974.
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