title: Sweet Taste-Sensing Receptors Expressed in Pancreatic β-Cells: Sweet Molecules Act as Biased Agonists.
abstract: The sweet taste receptors present in the taste buds are heterodimers comprised of T1R2 and T1R3. This receptor is also expressed in pancreatic β-cells. When the expression of receptor subunits is determined in β-cells by quantitative reverse transcription polymerase chain reaction, the mRNA expression level of T1R2 is extremely low compared to that of T1R3. In fact, the expression of T1R2 is undetectable at the protein level. Furthermore, knockdown of T1R2 does not affect the effect of sweet molecules, whereas knockdown of T1R3 markedly attenuates the effect of sweet molecules. Consequently, a homodimer of T1R3 functions as a receptor sensing sweet molecules in β-cells, which we designate as sweet taste-sensing receptors (STSRs). Various sweet molecules activate STSR in β-cells and augment insulin secretion. With regard to intracellular signals, sweet molecules act on STSRs and increase cytoplasmic Ca(2+) and/or cyclic AMP (cAMP). Specifically, when an STSR is stimulated by one of four different sweet molecules (sucralose, acesulfame potassium, sodium saccharin, or glycyrrhizin), distinct signaling pathways are activated. Patterns of changes in cytoplasmic Ca(2+) and/or cAMP induced by these sweet molecules are all different from each other. Hence, sweet molecules activate STSRs by acting as biased agonists.
authors.affiliation: Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
authors.affiliation: Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohtsu
authors.affiliation: Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Anya
authors.initials: A
authors.lastname: Medina
authors.affiliation: Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagasawa
keywords: Biased agonist; Calcium; Cyclic AMP; Insulin; Sweet taste receptor; β-Cell
references.citation: Adv Exp Med Biol. 2010;654:281-304
references.pmid: 20217503
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4692-6
references.pmid: 11917125
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15166-71
references.pmid: 14634208
references.citation: J Biol Chem. 1994 Apr 22;269(16):12190-5
references.pmid: 8163524
references.citation: Nature. 1992 Jun 18;357(6379):563-9
references.pmid: 1608467
references.citation: Eur J Cell Biol. 1998 Nov;77(3):253-61
references.pmid: 9860142
references.citation: PLoS One. 2012;7(4):e35380
references.pmid: 22536376
references.citation: Front Integr Neurosci. 2009 Jun 19;3:12
references.pmid: 19587847
references.citation: Comp Biochem Physiol A Comp Physiol. 1991;100(2):309-14
references.pmid: 1685952
references.citation: Sci Rep. 2012;2:496
references.pmid: 22773945
references.citation: Curr Pharm Des. 2006;12(35):4591-600
references.pmid: 17168764
references.citation: Biochem Biophys Res Commun. 2001 Apr 27;283(1):236-42
references.pmid: 11322794
references.citation: Nat Genet. 2001 May;28(1):58-63
references.pmid: 11326277
references.citation: Mamm Genome. 2001 Jan;12(1):13-6
references.pmid: 11178737
references.citation: J Neurosci. 2004 Sep 1;24(35):7674-80
references.pmid: 15342734
references.citation: Br J Pharmacol. 2012 Mar;165(6):1659-1669
references.pmid: 22023017
references.citation: Cell. 2003 Oct 31;115(3):255-66
references.pmid: 14636554
references.citation: Biochimie. 2013 Jul;95(7):1502-5
references.pmid: 23370115
references.citation: Cell. 2001 Aug 10;106(3):381-90
references.pmid: 11509186
references.citation: Adv Food Nutr Res. 2007;53:199-239
references.pmid: 17900500
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14258-63
references.pmid: 15353592
references.citation: Am J Physiol Cell Physiol. 2006 Aug;291(2):C237-44
references.pmid: 16510847
references.citation: Endocr J. 2014;61(2):119-31
references.pmid: 24200979
references.citation: FEBS Lett. 2002 Aug 28;526(1-3):1-4
references.pmid: 12208493
references.citation: J Biol Chem. 2005 Oct 7;280(40):34296-305
references.pmid: 16076846
references.citation: J Biol Chem. 2004 Oct 22;279(43):45068-75
references.pmid: 15299024
references.citation: Nat Neurosci. 2001 May;4(5):492-8
references.pmid: 11319557
references.citation: Diabetes Metab J. 2011 Oct;35(5):451-7
references.pmid: 22111035
references.citation: J Urol. 2011 Dec;186(6):2455-62
references.pmid: 22019168
references.citation: Nature. 2013 Mar 14;495(7440):223-6
references.pmid: 23467090
references.citation: Nature. 2000 Oct 26;407(6807):971-7
references.pmid: 11069170
references.citation: Cell. 2003 Feb 7;112(3):293-301
references.pmid: 12581520
references.citation: Nature. 2006 May 18;441(7091):354-7
references.pmid: 16633339
references.citation: Biochem Soc Trans. 2005 Feb;33(Pt 1):302-5
references.pmid: 15667333
references.citation: BMC Pulm Med. 2011 Jan 13;11:3
references.pmid: 21232137
references.citation: Endocr J. 2013;60(10):1191-206
references.pmid: 23933592
references.citation: Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):E524-32
references.pmid: 22315413
references.citation: Science. 2003 Aug 8;301(5634):850-3
references.pmid: 12869700
references.citation: PLoS One. 2009;4(4):e5106
references.pmid: 19352508
references.citation: PLoS One. 2013;8(1):e54500
references.pmid: 23336004
references.citation: Chem Senses. 2001 Sep;26(7):925-33
references.pmid: 11555487
references.citation: Pflugers Arch. 2007 Aug;454(5):759-76
references.pmid: 17468883
references.citation: Chem Senses. 2007 Jan;32(1):41-9
references.pmid: 17030556
references.citation: Chem Senses. 2003 Sep;28(7):573-9
references.pmid: 14578119