%0 Journal Article %1 Nakagawa2009 %A Nakagawa, Y. %A Nagasawa, M. %A Yamada, S. %A Hara, A. %A Mogami, H. %A Nikolaev, V. O. %A Lohse, M. J. %A Shigemura, N. %A Ninomiya, Y. %A Kojima, I. %D 2009 %J PLoS One %K & *Signal *Taste AMP/*metabolism Activation Animals Base C/metabolism Calcium/*metabolism Cell Chain Cyclic Cytoplasm/metabolism DNA Enzyme G-Protein-Coupled/*metabolism Insulin/*secretion Islets Kinase Langerhans/*metabolism/secretion Line Mice Polymerase Primers Protein Reaction Reverse Sequence Sucrose/analogs Transcriptase Transduction derivatives/pharmacology of Receptor %N 4 %P e5106 %T Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19352508 %V 4 %X 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.

@article{Nakagawa2009, abstract = {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.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Nakagawa, Y. and Nagasawa, M. and Yamada, S. and Hara, A. and Mogami, H. and Nikolaev, V. O. and Lohse, M. J. and Shigemura, N. and Ninomiya, Y. and Kojima, I.}, biburl = {https://www.bibsonomy.org/bibtex/2801c0c68b7bf38bb6c76805faab8dde9/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {d250f8177905a8fbeddbf84d9b02789c}, intrahash = {801c0c68b7bf38bb6c76805faab8dde9}, issn = {1932-6203 (Electronic)}, journal = {PLoS One}, keywords = {& *Signal *Taste AMP/*metabolism Activation Animals Base C/metabolism Calcium/*metabolism Cell Chain Cyclic Cytoplasm/metabolism DNA Enzyme G-Protein-Coupled/*metabolism Insulin/*secretion Islets Kinase Langerhans/*metabolism/secretion Line Mice Polymerase Primers Protein Reaction Reverse Sequence Sucrose/analogs Transcriptase Transduction derivatives/pharmacology of Receptor}, note = {Nakagawa, Yuko Nagasawa, Masahiro Yamada, Satoko Hara, Akemi Mogami, Hideo Nikolaev, Viacheslav O Lohse, Martin J Shigemura, Noriatsu Ninomiya, Yuzo Kojima, Itaru Research Support, Non-U.S. Gov't United States PloS one PLoS One. 2009;4(4):e5106. Epub 2009 Apr 8.}, number = 4, pages = {e5106}, shorttitle = {Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion}, timestamp = {2010-12-14T18:20:07.000+0100}, title = {Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19352508}, volume = 4, year = 2009 }