A novel variant of ionotropic glutamate receptor regulates somatostatin secretion from δ-cells of islets of Langerhans

Akiko Muroyama, Shunsuke Uehara, Shouki Yatsushiro, Noriko Echigo, Riyo Morimoto, Mitsuhiro Morita, Mitsuko Hayashi, Akitsugu Yamamoto, Duk Su Koh, Yoshinori Moriyama

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


Many metabolic factors affect the secretion of insulin from β-cells and glucagon from α-cells of the islets of Langerhans to regulate blood glucose. Somatostatin from δ-cells, considered a local inhibitor of islet function, reduces insulin and glucagon secretion by activating somatostatin receptors in islet cells. Somatostatin secretion from δ-cells is increased by high glucose via glucose metabolism in a similar way to insulin secretion from β-cells. However, it is unknown how low glucose triggers somatostatin secretion. Because L-glutamate is cosecreted with glucagon from α-cells under low-glucose conditions and acts as a primary intercellular messenger, we hypothesized that glutamate signaling triggers the secretion of somatostatin. In this study, we showed that δ-cells express GluR4c-flip, a newly identified splicing variant of GluR4, an (RS)-α-amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid (AMPA)-type ionotropic glutamate receptor of rat. After treatment with L-glutamate, AMPA, or kainate, secretion of somatostatin from isolated islets was significantly stimulated under low-glucose conditions. The glutamate-dependent somatostatin secretion was Ca2+ dependent and blocked by 6-cyano-7-nitroquinoxaline-2,3-dione. Somatostatin in turn inhibited the secretion of L-glutamate and glucagon from α-cells. These results indicate that L-glutamate triggers somatostatin secretion from δ-cells by way of the GluR4c-flip receptor under low-glucose conditions. The released somatostatin may complete the feedback inhibition of α-cells. Thus, α- and β-cells may conununicate with each other through L-glutamate and somatostatin signaling.

Original languageEnglish
Pages (from-to)1743-1753
Number of pages11
Issue number7
Publication statusPublished - Jul 2004

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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