1. A novel variant of ionotropic glutamate receptor regulates somatostatin secretion from delta-cells of islets of Langerhans.
- Author
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Muroyama, Akiko, Uehara, Shunsuke, Yatsushiro, Shouki, Echigo, Noriko, Morimoto, Riyo, Hayashi, Mitsuko, Moriyama, Yoshinori, Morita, Mitsuhiro, Yamamoto, Akitsugu, and Koh, Duk-Su
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SOMATOSTATIN , *ISLANDS of Langerhans , *GLUCOSE , *GLUCAGON , *METABOLISM , *INSULIN , *BLOOD sugar - Abstract
Many metabolic factors affect the secretion of insulin from beta-cells and glucagon from alpha-cells of the islets of Langerhans to regulate blood glucose. Somatostatin from delta-cells, considered a local inhibitor of islet function, reduces insulin and glucagon secretion by activating somatostatin receptors in islet cells. Somatostatin secretion from delta-cells is increased by high glucose via glucose metabolism in a similar way to insulin secretion from beta-cells. However, it is unknown how low glucose triggers somatostatin secretion. Because L-glutamate is cosecreted with glucagon from alpha-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 delta-cells express GluR4c-flip, a newly identified splicing variant of GluR4, an (RS)-alpha-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 Ca(2+) dependent and blocked by 6-cyano-7-nitroquinoxaline-2,3-dione. Somatostatin in turn inhibited the secretion of L-glutamate and glucagon from alpha-cells. These results indicate that L-glutamate triggers somatostatin secretion from delta-cells by way of the GluR4c-flip receptor under low-glucose conditions. The released somatostatin may complete the feedback inhibition of alpha-cells. Thus, alpha- and delta-cells may communicate with each other through L-glutamate and somatostatin signaling. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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