Diabetes Metab J.  2011 Oct;35(5):451-457. 10.4093/dmj.2011.35.5.451.

The Role of the Sweet Taste Receptor in Enteroendocrine Cells and Pancreatic beta-Cells

• Kojima I
• Nakagawa Y

• KMID: 1857499
• DOI: http://doi.org/10.4093/dmj.2011.35.5.451

Abstract

The sweet taste receptor is expressed in taste cells located in taste buds of the tongue. This receptor senses sweet substances in the oral cavity, activates taste cells, and transmits the taste signals to adjacent neurons. The sweet taste receptor is a heterodimer of two G protein-coupled receptors, T1R2 and T1R3. Recent studies have shown that this receptor is also expressed in the extragustatory system, including the gastrointestinal tract, pancreatic beta-cells, and glucose-responsive neurons in the brain. In the intestine, the sweet taste receptor regulates secretion of incretin hormones and glucose uptake from the lumen. In beta-cells, activation of the sweet taste receptor leads to stimulation of insulin secretion. Collectively, the sweet taste receptor plays an important role in recognition and metabolism of energy sources in the body.

Keyword

beta-cell; Calcium; Cyclic AMP; Glucose-dependent insulinotropic peptide; Glucagon-like peptide-1; Glucose incretin; Glucose transporter; Insulin; Sweet taste receptor

MeSH Terms

Brain
Calcium
Cyclic AMP
Enteroendocrine Cells
Gastric Inhibitory Polypeptide
Gastrointestinal Tract
Glucagon-Like Peptide 1
Glucose
Glucose Transport Proteins, Facilitative
Incretins
Insulin
Intestines
Mouth
Neurons
Taste Buds
Tongue
Calcium
Cyclic AMP
Gastric Inhibitory Polypeptide
Glucagon-Like Peptide 1
Glucose
Glucose Transport Proteins, Facilitative
Incretins
Insulin

Figure

• 

  Fig. 1 Structure of the sweet taste receptor. The sweet taste receptor consists of a heterodimer of the class C GPCRs, T1R2, and T1R3. Various sweet substances bind to different portions of the receptor.

• 

  Fig. 2 Effect of sucralose on [Ca2+]c, [cAMP]c, and PKC activation. (A) Epac-camp-expressing MIN6 cells loaded with fura-2 were incubated with 50 mM sucralose, and changes in [Ca2+]c (○) and [cAMP]c (•) were monitored. (B) MIN6 cells expressing MARCKS-GFP were incubated with 50 mM sucralose, and changes in the amount of MARCKS-GFP in the cytosol were monitored.

• 

  Fig. 3 Signaling system activated by the sweet taste receptor in β-cells. PLCβ2, phospholipase C-β2; cAMP, cyclic AMP; ER, endoplasmic reticulum.

Reference

1. Pierce-Shimomura JT, Faumont S, Gaston MR, Pearson BJ, Lockery SR. The homeobox gene lim-6 is required for distinct chemosensory representations in C. elegans. Nature. 2001. 410:694–698.

2. Clyne PJ, Warr CG, Carlson JR. Candidate taste receptors in Drosophila. Science. 2000. 287:1830–1834.

3. Temussi PA. Sweet, bitter and umami receptors: a complex relationship. Trends Biochem Sci. 2009. 34:296–302.

4. Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS. Mammalian sweet taste receptors. Cell. 2001. 106:381–390.

5. Pin JP, Galvez T, Prezeau L. Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors. Pharmacol Ther. 2003. 98:325–354.

6. Morini G, Bassoli A, Temussi PA. From small sweeteners to sweet proteins: anatomy of the binding sites of the human T1R2_T1R3 receptor. J Med Chem. 2005. 48:5520–5529.

7. Jiang P, Ji Q, Liu Z, Snyder LA, Benard LM, Margolskee RF, Max M. The cysteine-rich region of T1R3 determines responses to intensely sweet proteins. J Biol Chem. 2004. 279:45068–45075.

8. Xu H, Staszewski L, Tang H, Adler E, Zoller M, Li X. Different functional roles of T1R subunits in the heteromeric taste receptors. Proc Natl Acad Sci U S A. 2004. 101:14258–14263.

9. Jiang P, Cui M, Zhao B, Snyder LA, Benard LM, Osman R, Max M, Margolskee RF. Identification of the cyclamate interaction site within the transmembrane domain of the human sweet taste receptor subunit T1R3. J Biol Chem. 2005. 280:34296–34305.

10. McLaughlin SK, McKinnon PJ, Margolskee RF. Gustducin is a taste-cell-specific G protein closely related to the transducins. Nature. 1992. 357:563–569.

11. Wong GT, Gannon KS, Margolskee RF. Transduction of bitter and sweet taste by gustducin. Nature. 1996. 381:796–800.

12. Striem BJ, Pace U, Zehavi U, Naim M, Lancet D. Sweet tastants stimulate adenylate cyclase coupled to GTP-binding protein in rat tongue membranes. Biochem J. 1989. 260:121–126.

13. Trubey KR, Culpepper S, Maruyama Y, Kinnamon SC, Chaudhari N. Tastants evoke cAMP signal in taste buds that is independent of calcium signaling. Am J Physiol Cell Physiol. 2006. 291:C237–C244.

14. Rossler P, Kroner C, Freitag J, Noe J, Breer H. Identification of a phospholipase C beta subtype in rat taste cells. Eur J Cell Biol. 1998. 77:253–261.

15. Prawitt D, Monteilh-Zoller MK, Brixel L, Spangenberg C, Zabel B, Fleig A, Penner R. TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i. Proc Natl Acad Sci U S A. 2003. 100:15166–15171.

16. Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ. Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell. 2003. 112:293–301.

17. Damak S, Rong M, Yasumatsu K, Kokrashvili Z, Perez CA, Shigemura N, Yoshida R, Mosinger B Jr, Glendinning JI, Ninomiya Y, Margolskee RF. Trpm5 null mice respond to bitter, sweet, and umami compounds. Chem Senses. 2006. 31:253–264.

18. Dyer J, Salmon KS, Zibrik L, Shirazi-Beechey SP. Expression of sweet taste receptors of the T1R family in the intestinal tract and enteroendocrine cells. Biochem Soc Trans. 2005. 33(Pt 1):302–305.

19. Rozengurt N, Wu SV, Chen MC, Huang C, Sternini C, Rozengurt E. Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon. Am J Physiol Gastrointest Liver Physiol. 2006. 291:G792–G802.

20. Margolskee RF, Dyer J, Kokrashvili Z, Salmon KS, Ilegems E, Daly K, Maillet EL, Ninomiya Y, Mosinger B, Shirazi-Beechey SP. T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc Natl Acad Sci U S A. 2007. 104:15075–15080.

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

22. Ren X, Zhou L, Terwilliger R, Newton SS, de Araujo IE. Sweet taste signaling functions as a hypothalamic glucose sensor. Front Integr Neurosci. 2009. 3:12.

23. Hofer D, Puschel B, Drenckhahn D. Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin. Proc Natl Acad Sci U S A. 1996. 93:6631–6634.

24. Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, Max M, Margolskee RF. A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci. 2002. 5:1169–1176.

25. Dyer J, Salmon KS, Zibrik L, Shirazi-Beechey SP. Expression of sweet taste receptors of the T1R family in the intestinal tract and enteroendocrine cells. Biochem Soc Trans. 2005. 33(Pt 1):302–305.

26. Bezencon C, le Coutre J, Damak S. Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells. Chem Senses. 2007. 32:41–49.

27. Hass N, Schwarzenbacher K, Breer H. T1R3 is expressed in brush cells and ghrelin-producing cells of murine stomach. Cell Tissue Res. 2010. 339:493–504.

28. Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, Kim HH, Xu X, Chan SL, Juhaszova M, Bernier M, Mosinger B, Margolskee RF, Egan JM. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A. 2007. 104:15069–15074.

29. Gerspach AC, Steinert RE, Schonenberger L, Graber-Maier A, Beglinger C. The role of the gut sweet taste receptor in regulating GLP-1, PYY, and CCK release in humans. Am J Physiol Endocrinol Metab. 2011. 301:E317–E325.

30. Reimann F, Habib AM, Tolhurst G, Parker HE, Rogers GJ, Gribble FM. Glucose sensing in L cells: a primary cell study. Cell Metab. 2008. 8:532–539.

31. Renwick AG, Molinary SV. Sweet-taste receptors, low-energy sweeteners, glucose absorption and insulin release. Br J Nutr. 2010. 104:1415–1420.

32. Mace OJ, Affleck J, Patel N, Kellett GL. Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2. J Physiol. 2007. 582(Pt 1):379–392.

33. Mace OJ, Lister N, Morgan E, Shepherd E, Affleck J, Helliwell P, Bronk JR, Kellett GL, Meredith D, Boyd R, Pieri M, Bailey PD, Pettcrew R, Foley D. An energy supply network of nutrient absorption coordinated by calcium and T1R taste receptors in rat small intestine. J Physiol. 2009. 587(Pt 1):195–210.

34. Edlund H. Pancreas: how to get there from the gut? Curr Opin Cell Biol. 1999. 11:663–668.