Sweet taste receptor expressed in pancreatic beta-cells activates
the calcium and cyclic AMP signaling systems and stimulates insulin
secretion
Y. Nakagawa, M. Nagasawa, S. Yamada, A. Hara, H. Mogami, V. Nikolaev, M. Lohse, N. Shigemura, Y. Ninomiya, and I. Kojima. PLoS One, 4 (4):
e5106(2009)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..
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.
%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
}