Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.

BACKGROUND:Sweet taste receptor is expressed in the taste buds and enteroendocrine cells acting as a sugar sensor. We investigated the expression and function of the sweet taste receptor in MIN6 cells and mouse islets. METHODOLOGY/PRINCIPAL FINDINGS:The expression of the sweet taste receptor was det...

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Main Authors: Yuko Nakagawa, Masahiro Nagasawa, Satoko Yamada, Akemi Hara, Hideo Mogami, Viacheslav O Nikolaev, Martin J Lohse, Noriatsu Shigemura, Yuzo Ninomiya, Itaru Kojima
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2663034?pdf=render
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author Yuko Nakagawa
Masahiro Nagasawa
Satoko Yamada
Akemi Hara
Hideo Mogami
Viacheslav O Nikolaev
Martin J Lohse
Noriatsu Shigemura
Yuzo Ninomiya
Itaru Kojima
author_facet Yuko Nakagawa
Masahiro Nagasawa
Satoko Yamada
Akemi Hara
Hideo Mogami
Viacheslav O Nikolaev
Martin J Lohse
Noriatsu Shigemura
Yuzo Ninomiya
Itaru Kojima
author_sort Yuko Nakagawa
collection DOAJ
description BACKGROUND:Sweet taste receptor is expressed in the taste buds and enteroendocrine cells acting as a sugar sensor. We investigated the expression and function of the sweet taste receptor in MIN6 cells and mouse islets. METHODOLOGY/PRINCIPAL FINDINGS:The expression of the sweet taste receptor was determined by RT-PCR and immunohistochemistry. Changes in cytoplasmic Ca(2+) ([Ca(2+)](c)) and cAMP ([cAMP](c)) were monitored in MIN6 cells using fura-2 and Epac1-camps. Activation of protein kinase C was monitored by measuring translocation of MARCKS-GFP. Insulin was measured by radioimmunoassay. mRNA for T1R2, T1R3, and gustducin was expressed in MIN6 cells. In these cells, artificial sweeteners such as sucralose, succharin, and acesulfame-K increased insulin secretion and augmented secretion induced by glucose. Sucralose increased biphasic increase in [Ca(2+)](c). The second sustained phase was blocked by removal of extracellular calcium and addition of nifedipine. An inhibitor of inositol(1, 4, 5)-trisphophate receptor, 2-aminoethoxydiphenyl borate, blocked both phases of [Ca(2+)](c) response. The effect of sucralose on [Ca(2+)](c) was inhibited by gurmarin, an inhibitor of the sweet taste receptor, but not affected by a G(q) inhibitor. Sucralose also induced sustained elevation of [cAMP](c), which was only partially inhibited by removal of extracellular calcium and nifedipine. Finally, mouse islets expressed T1R2 and T1R3, and artificial sweeteners stimulated insulin secretion. CONCLUSIONS:Sweet taste receptor is expressed in beta-cells, and activation of this receptor induces insulin secretion by Ca(2+) and cAMP-dependent mechanisms.
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spelling doaj.art-0f66c5983d664586ae47caaccbb9fce22022-12-21T18:23:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0144e510610.1371/journal.pone.0005106Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.Yuko NakagawaMasahiro NagasawaSatoko YamadaAkemi HaraHideo MogamiViacheslav O NikolaevMartin J LohseNoriatsu ShigemuraYuzo NinomiyaItaru KojimaBACKGROUND:Sweet taste receptor is expressed in the taste buds and enteroendocrine cells acting as a sugar sensor. We investigated the expression and function of the sweet taste receptor in MIN6 cells and mouse islets. METHODOLOGY/PRINCIPAL FINDINGS:The expression of the sweet taste receptor was determined by RT-PCR and immunohistochemistry. Changes in cytoplasmic Ca(2+) ([Ca(2+)](c)) and cAMP ([cAMP](c)) were monitored in MIN6 cells using fura-2 and Epac1-camps. Activation of protein kinase C was monitored by measuring translocation of MARCKS-GFP. Insulin was measured by radioimmunoassay. mRNA for T1R2, T1R3, and gustducin was expressed in MIN6 cells. In these cells, artificial sweeteners such as sucralose, succharin, and acesulfame-K increased insulin secretion and augmented secretion induced by glucose. Sucralose increased biphasic increase in [Ca(2+)](c). The second sustained phase was blocked by removal of extracellular calcium and addition of nifedipine. An inhibitor of inositol(1, 4, 5)-trisphophate receptor, 2-aminoethoxydiphenyl borate, blocked both phases of [Ca(2+)](c) response. The effect of sucralose on [Ca(2+)](c) was inhibited by gurmarin, an inhibitor of the sweet taste receptor, but not affected by a G(q) inhibitor. Sucralose also induced sustained elevation of [cAMP](c), which was only partially inhibited by removal of extracellular calcium and nifedipine. Finally, mouse islets expressed T1R2 and T1R3, and artificial sweeteners stimulated insulin secretion. CONCLUSIONS:Sweet taste receptor is expressed in beta-cells, and activation of this receptor induces insulin secretion by Ca(2+) and cAMP-dependent mechanisms.http://europepmc.org/articles/PMC2663034?pdf=render
spellingShingle Yuko Nakagawa
Masahiro Nagasawa
Satoko Yamada
Akemi Hara
Hideo Mogami
Viacheslav O Nikolaev
Martin J Lohse
Noriatsu Shigemura
Yuzo Ninomiya
Itaru Kojima
Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.
PLoS ONE
title Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.
title_full Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.
title_fullStr Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.
title_full_unstemmed Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.
title_short Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.
title_sort sweet taste receptor expressed in pancreatic beta cells activates the calcium and cyclic amp signaling systems and stimulates insulin secretion
url http://europepmc.org/articles/PMC2663034?pdf=render
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