Electrophysiology of the pancreatic islet β-cell sweet taste receptor TIR3

  • Juan V. Sanchez-AndresEmail author
  • Willy J. Malaisse
  • Itaru Kojima
Signaling and cell physiology
Part of the following topical collections:
  1. Signaling and cell physiology


Over recent years, the presence of the sweet taste receptor TIR3 in rodent and human insulin-producing pancreatic islet β-cells was documented. The activation of this receptor by sweet-tasting sucralose mimics several biochemical and functional effects of d-glucose in the β-cells. The present study extends this analogy to the bioelectrical response of β-cells. In this respect, sucralose was inefficient in the absence of d-glucose, but induced on occasion electrical activity in mouse β-cells exposed to low non-stimulatory concentrations of the hexose and potentiated, in a concentration-related manner, the response to stimulatory concentrations of d-glucose. These data indicate that sucralose, acting as an agonist of the TIR3 receptor, exerts an excitatory effect upon pancreatic β-cell bioelectrical activity.


Bioelectrical activity Pancreatic islet β-cells Sweet taste receptor TIR3 Sucralose 



  1. 1.
    Avrahami D, Klochendler A, Dor Y, Glaser B (2017) Beta cell heterogeneity: an evolving concept. Diabetologia 60:1363–1369CrossRefGoogle Scholar
  2. 2.
    Bonner-Weir S, Aguayo-Mazzucato C (2016) Pancreatic β-cell heterogeneity revisited. Nature 535:365–366CrossRefGoogle Scholar
  3. 3.
    Buzsáki G, Mizuseki K (2014) The log-dynamic brain: how skewed distributions affect network operations. Nat Rev Neurosci 15(4):264–278CrossRefGoogle Scholar
  4. 4.
    Fichaux F, Marchand J, Yaylali B, Leclercq-Meyer V, Catala J, Malaisse WJ (1991) Altered anomeric specificity of glucose-induced insulin release in rabbits with duct-ligated pancreas. Int J Pancreatol 8:151–167Google Scholar
  5. 5.
    Hellerstrom C, Petersson B, Hellman B (1960) Some properties of the β cells in the islet of Langerhans studied with regard to the position of the cells. Acta Endocrinol 34:449–456CrossRefGoogle Scholar
  6. 6.
    Henquin JC (2012) Do pancreatic β-cells “taste” nutrients to secrete insulin? Sci Signal 5:pe36CrossRefGoogle Scholar
  7. 7.
    Holz G, Chepurny OG, Leech CA, Song W-J, Hussain MA (2015) Molecular basis of cAMP signaling in pancreatic β-cells. In: Islets of Langerhans, 2nd ed., Md. Shahidul Islam ed, chapter 20. Springer, Dordrecht, pp. 565–603.
  8. 8.
    Kalwat MA, Cobb MH (2017) Mechanisms of the amplifying pathway of insulin secretion in the β cell. Pharmacol Ther 179:17–30CrossRefGoogle Scholar
  9. 9.
    Kojima I, Nakagawa Y (2011) The role of the sweet taste receptor in enteroendocrine cells and pancreatic β-cells. Diabetes Metab J 34:451–457CrossRefGoogle Scholar
  10. 10.
    Kojima I, Nakagawa Y, Ohtsu Y, Medina A, Nagasawa M (2014) Sweet taste-sensing receptors expressed in pancreatic β-cells: sweet molecules act as biased agonists. Endocrinol Metab 29:12–19CrossRefGoogle Scholar
  11. 11.
    Kojima I, Nakagawa Y, Ohtsu Y, Hamano K, Medina J, Nagasawa M (2015) Return of the glucoreceptor: glucose activates the glucose-sensing receptor T1R3 and facilitates metabolism in pancreatic β-cells. J Diabetes Invest 6:256–263CrossRefGoogle Scholar
  12. 12.
    Leclercq-Meyer V, Marchand J, Malaisse WJ (1987a) Anomeric specificity of the insulin and glucagon secretory response to D-glucose in lean and obese Zucker rats. Pancreas 2:645–652CrossRefGoogle Scholar
  13. 13.
    Leclercq-Meyer V, Marchand J, Malaisse WJ (1987b) Alteration of the insulin secretory response to D-glucose anomers in diabetic BB rats. Med Sci Res 15:1535–1536Google Scholar
  14. 14.
    Leclercq-Meyer V, Marchand J, Malaisse WJ (1991) Attenuated anomeric difference of glucose-induced insulin release in the perfused pancreas of diazoxide-treated rats. Horm Metab Res 23:257–261CrossRefGoogle Scholar
  15. 15.
    Li L, Ohtsu Y, Nakagawa Y, Masuda K, Kojima I (2016) Sucralose, an activator of the glucose-sensing receptor, increases ATP by calcium-dependent and -independent mechanisms. Endocr J 63(8):715–725CrossRefGoogle Scholar
  16. 16.
    Malaisse WJ (1987) Insulin release: the glucoreceptor myth. Med Sci Res 15:65–67Google Scholar
  17. 17.
    Malaisse WJ (1991) The anomeric malaise: a manifestation of B-cell glucotoxicity. Horm Metab Res 23:307–311CrossRefGoogle Scholar
  18. 18.
    Malaisse WJ (2014) Insulin release: the receptor hypothesis. Diabetologia 57:1287–1290CrossRefGoogle Scholar
  19. 19.
    Malaisse WJ, Sener A, Herchuelz A, Hutton JC (1979) Insulin release: the fuel hypothesis. Metabolism 28:373–386CrossRefGoogle Scholar
  20. 20.
    Malaisse WJ, Sener A, Malaisse-Lagae F (1981) Insulin release: reconciliation of the receptor and metabolic hypotheses. Nutrient receptors in islet cells. Mol Cell Biochem 37:157–165CrossRefGoogle Scholar
  21. 21.
    Malaisse WJ, Strange G, Kojima I (2014) Presence of the sweet taste TIR3 receptor in human and rat pancreatic islet cells. Abstract Book Autumn Meeting Belg Soc Physiol Pharmacol: P-02.
  22. 22.
    Malaisse-Lagae F, Malaisse WJ (1986) Abnormal identification of the sweet taste of D-glucose anomers. Diabetologia 29:344–345CrossRefGoogle Scholar
  23. 23.
    Medina J, Nakagawa Y, Nagasawa M, Fernandez A, Sakaguchi K, Kitaguchi T, Kojima I (2016) Positive allosteric modulation of the calcium-sensing receptor by physiological concentrations of glucose. J Biol Chem 291(44):23126–23135CrossRefGoogle Scholar
  24. 24.
    Nakagawa Y, Nagasawa M, Yamada S, Hara A, Mogami H, Nikolaev VO, Lohse MJ, Shigemura N, Ninomiya Y, Kojima I (2009) Sweet taste receptor expressed in pancreatic beta-cells activate the calcium and cyclic AMP signaling systems and stimulate insulin secretion. PLoS One 4:e5106CrossRefGoogle Scholar
  25. 25.
    Nakagawa Y, Nagasawa M, Mogani H, Lohse M, Ninomiya Y, Kojima I (2013a) Multimodel function of the sweet taste receptor expressed in pancreatic β-cells: generation of diverse patterns of intracellular signals by sweet agonists. Endocr J 60:1191–1206CrossRefGoogle Scholar
  26. 26.
    Nakagawa Y, Ohtsu Y, Nagasawa M, Shibata H, Kojima I (2013b) Glucose promotes its own metabolism by acting on the cell-surface glucose-sensing receptor TIR3. Endocr J 10:1507Google Scholar
  27. 27.
    Nakagawa Y, Nagasawa M, Medina J, Kojima I (2015) Glucose evokes rapid Ca2+ and cyclic AMP signals by activating the cell-surface glucose-sensing receptor in pancreatic β-cells. PLoS One 10(12):e0144053CrossRefGoogle Scholar
  28. 28.
    Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJP, Zuker CS (2001) Mammalian sweet taste receptors. Cell 106(3):381–390CrossRefGoogle Scholar
  29. 29.
    Niki A, Niki H, Niki I, Kunoh Y (1988) Insulin release by glucose anomers in a rat model of non-insulin-dependent diabetes. Diabetologia 31:65–67Google Scholar
  30. 30.
    Niki A, Niki H, Hashioka T (1989) Receptors of paraneurons, with special reference to glucoreceptors. Arch Histol Cytol 52(supl):33–38CrossRefGoogle Scholar
  31. 31.
    Roper SD (2007) Signal transduction and information processing in mammalian taste buds. Pflugers Arch 454:759–776CrossRefGoogle Scholar
  32. 32.
    Rovira A, Garrotte FJ, Valverde I, Malaisse WJ (1987) Anomeric specificity of glucose-induced insulin release in normal and diabetic subjects. Diab Res 5:119–124Google Scholar
  33. 33.
    Sanchez-Andres JV, Ripoll C, Soria B (1988) Evidence that muscarinic potentiation of insulin release is initiated by an early transient calcium entry. FEBS Lett 231:143–147CrossRefGoogle Scholar
  34. 34.
    Sener A, Malaisse WJ (1980) L-leucine and a nonmetabolized analogue activate glutamate dehydrogenase. Nature 288:187–189CrossRefGoogle Scholar
  35. 35.
    Temussi P (2007) The sweet taste receptor: a single receptor with multiple sites and modes of interaction. Adv Food Nutr Res 53:199–239CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of MedicineUniversitat Jaume 1CastellonSpain
  2. 2.Department of BiochemistryUniversité Libre de BruxellesBrusselsBelgium
  3. 3.Institute for Molecular and Cellular RegulationGunma UniversityMaebashiJapan

Personalised recommendations