title: AMPA receptors regulate exocytosis and insulin release in pancreatic β cells.
abstract: Ionotropic glutamate receptors (iGluRs) are expressed in islets and insulinoma cells and involved in insulin secretion. However, the exact roles that iGluRs play in β cells remain unclear. Here, we demonstrated that GluR2-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) were expressed in mouse β cells. Glutamate application increased both cytosolic calcium and the number of docked insulin-containing granules, which resulted in augmentation of depolarization-induced exocytosis and high-glucose-stimulated insulin release. While glutamate application directly depolarized β cells, it also induced an enormous depolarization when K(ATP) channels were available. Glutamate application reduced the conductance of K(ATP) channels and increased voltage oscillations. Moreover, actions of AMPARs were absent in Kir6.2 knock-out mice. The effects of AMPARs on K(ATP) channels were mediated by cytosolic cGMP. Taken together, our experiments uncovered a novel mechanism by which AMPARs participate in insulin release.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, P. R. China.
authors.forename: Zhen-Yong
authors.initials: ZY
authors.lastname: Wu
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Zhu
authors.forename: Na
authors.initials: N
authors.lastname: Zou
authors.forename: Lidija K
authors.initials: LK
authors.lastname: Bombek
authors.forename: Chong-Yu
authors.initials: CY
authors.lastname: Shao
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.forename: Marjan
authors.initials: M
authors.lastname: Rupnik
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism* / Q000502:physiology; D022142:Secretory Vesicles / Q000378:metabolism; D000099161:Kcnj11 Channel
chemical_list: D002118:Calcium; D006152:Cyclic GMP; D018698:Glutamic Acid; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D018091:Receptors, AMPA; D000099161:Kcnj11 Channel; C104722:glutamate receptor ionotropic, AMPA 2