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What Does Diabetes “Taste” Like?

  • Pathogenesis of Type 2 Diabetes and Insulin Resistance (RM Watanabe, Section Editor)
  • Published:
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Abstract

The T1R2 (taste type 1 receptor, member 2)/T1R3 (taste type 1 receptor, member 3) sweet taste receptor is expressed in taste buds on the tongue, where it allows the detection of energy-rich carbohydrates of food. This single receptor responds to all compounds perceived as sweet by humans, including natural sugars and natural and artificial sweeteners. Importantly, the T1R2/T1R3 sweet taste receptor is also expressed in extra-oral tissues, including the stomach, pancreas, gut, liver, and brain. Although its physiological role remains to be established in numerous organs, T1R2/T1R3 is suspected to be involved in the regulation of metabolic processes, such as sugar sensing, glucose homeostasis, and satiety hormone release. In this review, the physiological role of the sweet taste receptor in taste perception and metabolic regulation is discussed by focusing on dysfunctions leading to diabetes. Current knowledge of T1R2/T1R3 inhibitors making this receptor a promising therapeutic target for the treatment of type 2 diabetes is also summarized and discussed.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E. Human receptors for sweet and umami taste. Proc Natl Acad Sci U S A. 2002;99(7):4692–6. doi:10.1073/pnas.072090199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS. Mammalian sweet taste receptors. Cell. 2001;106(3):381–90.

    Article  CAS  PubMed  Google Scholar 

  3. Zhao GQ, Zhang Y, Hoon MA, Chandrashekar J, Erlenbach I, Ryba NJ, et al. The receptors for mammalian sweet and umami taste. Cell. 2003;115(3):255–66.

    Article  CAS  PubMed  Google Scholar 

  4. Pin JP, Kniazeff J, Binet V, Liu J, Maurel D, Galvez T, et al. Activation mechanism of the heterodimeric GABA(B) receptor. Biochem Pharmacol. 2004;68(8):1565–72. doi:10.1016/j.bcp.2004.06.035.

    Article  CAS  PubMed  Google Scholar 

  5. Jiang P, Ji Q, Liu Z, Snyder LA, Benard LM, Margolskee RF, et al. The cysteine-rich region of T1R3 determines responses to intensely sweet proteins. J Biol Chem. 2004;279(43):45068–75. doi:10.1074/jbc.M406779200.

    Article  CAS  PubMed  Google Scholar 

  6. Poirier N, Roudnitzky N, Brockhoff A, Belloir C, Maison M, Thomas-Danguin T, et al. Efficient production and characterization of the sweet-tasting brazzein secreted by the yeast Pichia pastoris. J Agric Food Chem. 2012;60(39):9807–14. doi:10.1021/jf301600m.

    Article  CAS  PubMed  Google Scholar 

  7. Ariyasu T, Matsumoto S, Kyono F, Hanaya T, Arai S, Ikeda M, et al. Taste receptor T1R3 is an essential molecule for the cellular recognition of the disaccharide trehalose. In Vitro Cell Dev Biol Anim. 2003;39(1-2):80–8. doi:10.1290/1543-706X(2003)039<0080:TRTIAE>2.0.CO;2.

    Article  CAS  PubMed  Google Scholar 

  8. Maitrepierre E, Sigoillot M, Le Pessot L, Briand L. Recombinant expression, in vitro refolding, and biophysical characterization of the N-terminal domain of T1R3 taste receptor. Protein Expr Purif. 2012;83(1):75–83. doi:10.1016/j.pep.2012.03.006.

    Article  CAS  PubMed  Google Scholar 

  9. Nie Y, Vigues S, Hobbs JR, Conn GL, Munger SD. Distinct contributions of T1R2 and T1R3 taste receptor subunits to the detection of sweet stimuli. Curr Biol. 2005;15(21):1948–52. doi:10.1016/j.cub.2005.09.037.

    Article  CAS  PubMed  Google Scholar 

  10. Damak S, Rong M, Yasumatsu K, Kokrashvili Z, Varadarajan V, Zou S, et al. Detection of sweet and umami taste in the absence of taste receptor T1r3. Science. 2003;301(5634):850–3. doi:10.1126/science.1087155.

    Article  CAS  PubMed  Google Scholar 

  11. Behrens M, Meyerhof W, Hellfritsch C, Hofmann T. Sweet and umami taste: natural products, their chemosensory targets, and beyond. Angew Chem Int Ed Engl. 2011;50(10):2220–42. doi:10.1002/anie.201002094.

    Article  CAS  PubMed  Google Scholar 

  12. 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(39):14258–63. doi:10.1073/pnas.0404384101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tizzano M, Dvoryanchikov G, Barrows JK, Kim S, Chaudhari N, Finger TE. Expression of Galpha14 in sweet-transducing taste cells of the posterior tongue. BMC Neurosci. 2008;9:110. doi:10.1186/1471-2202-9-110.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Eny KM, Wolever TM, Corey PN, El-Sohemy A. Genetic variation in TAS1R2 (Ile191Val) is associated with consumption of sugars in overweight and obese individuals in 2 distinct populations. Am J Clin Nutr. 2010;92(6):1501–10. doi:10.3945/ajcn.2010.29836.

    Article  CAS  PubMed  Google Scholar 

  15. Dias AG, Eny KM, Cockburn M, Chiu W, Nielsen DE, Duizer L, et al. Variation in the TAS1R2 gene, sweet taste perception and intake of sugars. J Nutrigenet Nutrigenomics. 2015;8(2):81–90. doi:10.1159/000430886.

    Article  CAS  PubMed  Google Scholar 

  16. Fushan AA, Simons CT, Slack JP, Manichaikul A, Drayna D. Allelic polymorphism within the TAS1R3 promoter is associated with human taste sensitivity to sucrose. Curr Biol. 2009;19(15):1288–93. doi:10.1016/j.cub.2009.06.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fushan AA, Simons CT, Slack JP, Drayna D. Association between common variation in genes encoding sweet taste signaling components and human sucrose perception. Chem Senses. 2010;35(7):579–92. doi:10.1093/chemse/bjq063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gondivkar SM, Indurkar A, Degwekar S, Bhowate R. Evaluation of gustatory function in patients with diabetes mellitus type 2. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108(6):876–80. doi:10.1016/j.tripleo.2009.08.015.

    Article  PubMed  Google Scholar 

  19. Wasalathanthri S, Hettiarachchi P, Prathapan S. Sweet taste sensitivity in pre-diabetics, diabetics and normoglycemic controls: a comparative cross sectional study. BMC Endocr Disord. 2014;14:67. doi:10.1186/1472-6823-14-67. The results presented in this paper confirmed a decrease in taste response for diabetics and showed a taste response for pre-diabetic as an intermediate between diabetic and normoglycemic patients.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Khobragade RS, Wakode SL, Kale AH. Physiological taste threshold in type 1 diabetes mellitus. Indian J Physiol Pharmacol. 2012;56(1):42–7.

    CAS  PubMed  Google Scholar 

  21. Tepper BJ, Hartfiel LM, Schneider SH. Sweet taste and diet in type II diabetes. Physiol Behav. 1996;60(1):13–8.

    Article  CAS  PubMed  Google Scholar 

  22. Fabian TK, Beck A, Fejerdy P, Hermann P, Fabian G. Molecular mechanisms of taste recognition: considerations about the role of saliva. Int J Mol Sci. 2015;16(3):5945–74. doi:10.3390/ijms16035945.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Neyraud E. Role of saliva in oral food perception. Monogr Oral Sci. 2014;24:61–70. doi:10.1159/000358789.

    Article  PubMed  Google Scholar 

  24. Ben-Aryeh H, Cohen M, Kanter Y, Szargel R, Laufer D. Salivary composition in diabetic patients. J Diabet Complications. 1988;2(2):96–9.

    Article  CAS  PubMed  Google Scholar 

  25. Fabian TK, Fejerdy P, Csermely P. Salivary genomics, transcriptomics and proteomics: the emerging concept of the oral ecosystem and their use in the early diagnosis of cancer and other diseases. Curr Genomics. 2008;9(1):11–21. doi:10.2174/138920208783884900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Koscielniak D, Jurczak A, Zygmunt A, Krzysciak W. Salivary proteins in health and disease. Acta Biochim Pol. 2012;59(4):451–7.

    CAS  PubMed  Google Scholar 

  27. Falchi M, El-Sayed Moustafa JS, Takousis P, Pesce F, Bonnefond A, Andersson-Assarsson JC et al. Low copy number of the salivary amylase gene predisposes to obesity. Nat Genet. 2014;46(5):492-7. doi:10.1038/ng.2939. Using 6200 subjects, the authors identified an association between a low copy number variants of the salivary amylase gene ( AMY1 ) with high body mass index and obesity risk.

  28. Mejia-Benitez MA, Bonnefond A, Yengo L, Huyvaert M, Dechaume A, Peralta-Romero J, et al. Beneficial effect of a high number of copies of salivary amylase AMY1 gene on obesity risk in Mexican children. Diabetologia. 2015;58(2):290–4. doi:10.1007/s00125-014-3441-3.

    Article  CAS  PubMed  Google Scholar 

  29. Indira M, Chandrashekar P, Kattappagari KK, Chandra LP, Chitturi RT, Bv RR. Evaluation of salivary glucose, amylase, and total protein in type 2 diabetes mellitus patients. Indian J Dent Res. 2015;26(3):271–5. doi:10.4103/0970-9290.162883.

    Article  CAS  PubMed  Google Scholar 

  30. Oxford GE, Tayari L, Barfoot MD, Peck AB, Tanaka Y, Humphreys-Beher MG. Salivary EGF levels reduced in diabetic patients. J Diabetes Complications. 2000;14(3):140–5.

    Article  CAS  PubMed  Google Scholar 

  31. Morris-Wiman J, Sego R, Brinkley L, Dolce C. The effects of sialoadenectomy and exogenous EGF on taste bud morphology and maintenance. Chem Senses. 2000;25(1):9–19.

    Article  CAS  PubMed  Google Scholar 

  32. Nagy A, Nagashima H, Cha S, Oxford GE, Zelles T, Peck AB, et al. Reduced oral wound healing in the NOD mouse model for type 1 autoimmune diabetes and its reversal by epidermal growth factor supplementation. Diabetes. 2001;50(9):2100–4.

    Article  CAS  PubMed  Google Scholar 

  33. Kerr M, Lee A, Wang PL, Purushotham KR, Chegini N, Yamamoto H, et al. Detection of insulin and insulin-like growth factors I and II in saliva and potential synthesis in the salivary glands of mice. Effects of type 1 diabetes mellitus. Biochem Pharmacol. 1995;49(10):1521–31.

    Article  CAS  PubMed  Google Scholar 

  34. Takai S, Yasumatsu K, Inoue M, Iwata S, Yoshida R, Shigemura N, et al. Glucagon-like peptide-1 is specifically involved in sweet taste transmission. FASEB J. 2015;29(6):2268–80. doi:10.1096/fj.14-265355.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Cai H, Maudsley S, Martin B. What is the role of metabolic hormones in taste buds of the tongue. Front Horm Res. 2014;42:134–46. doi:10.1159/000358322.

    Article  PubMed  Google Scholar 

  36. Calvo SS, Egan JM. The endocrinology of taste receptors. Nat Rev Endocrinol. 2015;11(4):213–27. doi:10.1038/nrendo.2015.7.

    CAS  PubMed  Google Scholar 

  37. Kubasova N, Burdakov D, Domingos AI. Sweet and low on leptin: hormonal regulation of sweet taste buds. Diabetes. 2015;64(11):3651–2. doi:10.2337/dbi15-0004.

    Article  CAS  PubMed  Google Scholar 

  38. Yoshida R, Noguchi K, Shigemura N, Jyotaki M, Takahashi I, Margolskee RF et al. Leptin suppresses mouse taste cell responses to sweet compounds. Diabetes. 2015;64(11):3751-62. doi:10.2337/db14-1462. This paper shows that leptin selectively suppresses sweet taste perception, but not other perceptions, through the inhibition of K ATP channel co-expressed in the same taste cells.

  39. Murovets VO, Bachmanov AA, Zolotarev VA. Impaired glucose metabolism in mice lacking the Tas1r3 taste receptor gene. PLoS One. 2015;10(6):e0130997. doi:10.1371/journal.pone.0130997.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Young RL, Sutherland K, Pezos N, Brierley SM, Horowitz M, Rayner CK, et al. Expression of taste molecules in the upper gastrointestinal tract in humans with and without type 2 diabetes. Gut. 2009;58(3):337–46. doi:10.1136/gut.2008.148932.

    Article  CAS  PubMed  Google Scholar 

  41. Bezencon C, le Coutre J, Damak S. Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells. Chem Senses. 2007;32(1):41–9. doi:10.1093/chemse/bjl034.

    Article  CAS  PubMed  Google Scholar 

  42. Dyer J, Vayro S, King TP, Shirazi-Beechey SP. Glucose sensing in the intestinal epithelium. Eur J Biochem. 2003;270(16):3377–88.

    Article  CAS  PubMed  Google Scholar 

  43. Symonds EL, Peiris M, Page AJ, Chia B, Dogra H, Masding A, et al. Mechanisms of activation of mouse and human enteroendocrine cells by nutrients. Gut. 2015;64(4):618–26. doi:10.1136/gutjnl-2014-306834.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A. 2007;104(38):15069–74. doi:10.1073/pnas.0706890104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Margolskee RF, Dyer J, Kokrashvili Z, Salmon KS, Ilegems E, Daly K, et al. T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc Natl Acad Sci U S A. 2007;104(38):15075–80. doi:10.1073/pnas.0706678104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Steinert RE, Gerspach AC, Gutmann H, Asarian L, Drewe J, Beglinger C. The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Clin Nutr. 2011;30(4):524–32. doi:10.1016/j.clnu.2011.01.007.

    Article  CAS  PubMed  Google Scholar 

  47. Shirazi-Beechey SP, Daly K, Al-Rammahi M, Moran AW, Bravo D. Role of nutrient-sensing taste 1 receptor (T1R) family members in gastrointestinal chemosensing. Br J Nutr. 2014;111 Suppl 1:S8–S15. doi:10.1017/S0007114513002286.

    Article  CAS  PubMed  Google Scholar 

  48. Young RL, Chia B, Isaacs NJ, Ma J, Khoo J, Wu T, et al. Disordered control of intestinal sweet taste receptor expression and glucose absorption in type 2 diabetes. Diabetes. 2013;62(10):3532–41. doi:10.2337/db13-0581. This study shows that intestinal T1R2 is less expressed in the presence of glucose for healthy subjects. In parallel, this downregulation is not observed in type 2 diabetes patients.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Swartz TD, Duca FA, de Wouters T, Sakar Y, Covasa M. Up-regulation of intestinal type 1 taste receptor 3 and sodium glucose luminal transporter-1 expression and increased sucrose intake in mice lacking gut microbiota. Br J Nutr. 2012;107(5):621–30. doi:10.1017/S0007114511003412.

    Article  CAS  PubMed  Google Scholar 

  50. Zhu X, He L, McCluskey LP. Ingestion of bacterial lipopolysaccharide inhibits peripheral taste responses to sucrose in mice. Neuroscience. 2014;258:47–61. doi:10.1016/j.neuroscience.2013.10.072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514(7521):181–6. doi:10.1038/nature13793.

    CAS  PubMed  Google Scholar 

  52. Nakagawa Y, Ohtsu Y, Nagasawa M, Shibata H, Kojima I. Glucose promotes its own metabolism by acting on the cell-surface glucose-sensing receptor T1R3. Endocr J. 2014;61(2):119–31.

    Article  CAS  PubMed  Google Scholar 

  53. Kyriazis GA, Soundarapandian MM, Tyrberg B. Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion. Proc Natl Acad Sci U S A. 2012;109(8):E524–32. doi:10.1073/pnas.1115183109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Malaisse WJ, Vanonderbergen A, Louchami K, Jijakli H, Malaisse-Lagae F. Effects of artificial sweeteners on insulin release and cationic fluxes in rat pancreatic islets. Cell Signal. 1998;10(10):727–33.

    Article  CAS  PubMed  Google Scholar 

  55. Kojima I, Nakagawa Y, Hamano K, Medina J, Li L, Nagasawa M. Glucose-sensing receptor T1R3: a new signaling receptor activated by glucose in pancreatic beta-cells. Biol Pharm Bull. 2015;38(5):674–9. doi:10.1248/bpb.b14-00895. This study demonstrates that in pancreatic cells, T1R3 acts as a glucose-sensing receptor, involved in glucose-induce insulin secretion.

    Article  CAS  PubMed  Google Scholar 

  56. Medina A, Nakagawa Y, Ma J, Li L, Hamano K, Akimoto T, et al. Expression of the glucose-sensing receptor T1R3 in pancreatic islet: changes in the expression levels in various nutritional and metabolic states. Endocr J. 2014;61(8):797–805. This paper highlights that T1R3 expression is modulated by the nutritional and metabolic states. A higher T1R3 expression is observed in beta cells in fasting condition.

    Article  CAS  PubMed  Google Scholar 

  57. Nakagawa Y, Nagasawa M, Mogami H, Lohse M, Ninomiya Y, Kojima I. Multimodal function of the sweet taste receptor expressed in pancreatic beta-cells: generation of diverse patterns of intracellular signals by sweet agonists. Endocr J. 2013;60(10):1191–206. This paper demonstrates that in pancreatic cells, the sweet taste receptor generates distinct patterns of intracellular signal following the sweetener used for its activation.

    Article  CAS  PubMed  Google Scholar 

  58. Kyriazis GA, Smith KR, Tyrberg B, Hussain T, Pratley RE. Sweet taste receptors regulate basal insulin secretion and contribute to compensatory insulin hypersecretion during the development of diabetes in male mice. Endocrinology. 2014;155(6):2112–21. doi:10.1210/en.2013-2015. This key study reveals that elevated glucose level reduces T1R2 expression in human pancreatic islet. Both pancreatic T1R2 and T1R3 present a lower expression level in obese or diabetic mouse model associated with an insulin hypersecretion. The insulin hypersecretion is also observed in T1R2 knockout mice in fasting condition.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Hardy ML, Coulter I, Venuturupalli S, Roth EA, Favreau J, Morton SC, et al. Ayurvedic interventions for diabetes mellitus: a systematic review. Evid Rep Technol Assess (Summ). 2001;41:2.

    Google Scholar 

  60. Galindo-Cuspinera V, Breslin PA. The liaison of sweet and savory. Chem Senses. 2006;31(3):221–5. doi:10.1093/chemse/bjj022.

    Article  CAS  PubMed  Google Scholar 

  61. Jiang P, Cui M, Zhao B, Liu Z, Snyder LA, Benard LM, et al. Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste. J Biol Chem. 2005;280(15):15238–46. doi:10.1074/jbc.M414287200.

    Article  CAS  PubMed  Google Scholar 

  62. Sanematsu K, Kusakabe Y, Shigemura N, Hirokawa T, Nakamura S, Imoto T, et al. Molecular mechanisms for sweet-suppressing effect of gymnemic acids. J Biol Chem. 2014;289(37):25711–20. doi:10.1074/jbc.M114.560409.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Sigoillot M, Brockhoff A, Meyerhof W, Briand L. Sweet-taste-suppressing compounds: current knowledge and perspectives of application. Appl Microbiol Biotechnol. 2012;96(3):619–30. doi:10.1007/s00253-012-4387-3.

    Article  CAS  PubMed  Google Scholar 

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  1. Centre des Sciences du Goût et de l’Alimentation, INRA, CNRS, Université de Bourgogne - Franche-Comté, Dijon, 21000, France

    Fabrice Neiers, Marie-Chantal Canivenc-Lavier & Loïc Briand

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  1. Fabrice Neiers
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This article is part of the Topical Collection on Pathogenesis of Type 2 Diabetes and Insulin Resistance

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Neiers, F., Canivenc-Lavier, MC. & Briand, L. What Does Diabetes “Taste” Like?. Curr Diab Rep 16, 49 (2016). https://doi.org/10.1007/s11892-016-0746-2

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