A novel variant of ionotropic glutamate receptor regulates somatostatin secretion from delta-cells of islets of Langerhans.
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.
Muroyama
Akiko
A
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan. moriyama@pheasant.pharm.okayama-u.ac.jp
Uehara
Shunsuke
S
Yatsushiro
Shouki
S
Echigo
Noriko
N
Morimoto
Riyo
R
Morita
Mitsuhiro
M
Hayashi
Mitsuko
M
Yamamoto
Akitsugu
A
Koh
Duk-Su
DS
Moriyama
Yoshinori
Y
D000818:Animals; D046508:Culture Techniques; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005934:Glucagon / Q000037:antagonists & inhibitors; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology; D006728:Hormones / Q000378:metabolism* / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017470:Receptors, Glutamate / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D006728:Hormones; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; C104724:glutamate receptor ionotropic, AMPA 4; D018698:Glutamic Acid; D013004:Somatostatin; D005934:Glucagon