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.


RESULTS
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.
Nakagawa
Yuko
Y
Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
Nagasawa
Masahiro
M
Yamada
Satoko
S
Hara
Akemi
A
Mogami
Hideo
H
Nikolaev
Viacheslav O
VO
Lohse
Martin J
MJ
Shigemura
Noriatsu
N
Ninomiya
Yuzo
Y
Kojima
Itaru
I
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers; D004789:Enzyme Activation; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013395:Sucrose / Q000031:analogs & derivatives / Q000494:pharmacology; D013649:Taste
D017931:DNA Primers; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D013395:Sucrose; C026285:trichlorosucrose; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium