Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity

Koenraad Philippaert; Andy Pironet; Margot Mesuere; William Sones; Laura Vermeiren; Sara Kerselaers; Sílvia Pinto; Andrei Segal; Nancy Antoine; Conny Gysemans; Jos Laureys; Katleen Lemaire; Patrick Gilon; Eva Cuypers; Jan Tytgat; Chantal Mathieu; Frans Schuit; Patrik Rorsman; Karel Talavera; Thomas Voets; Rudi Vennekens

doi:10.1038/ncomms14733

Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity

Koenraad Philippaert, Andy Pironet, Margot Mesuere, William Sones, Laura Vermeiren, Sara Kerselaers, Sílvia Pinto, Andrei Segal, Nancy Antoine, Conny Gysemans, Jos Laureys, Katleen Lemaire, Patrick Gilon, Eva Cuypers, Jan Tytgat, Chantal Mathieu, Frans Schuit, Patrik Rorsman, Karel Talavera, Thomas VoetsRudi Vennekens^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Steviol glycosides (SGs), such as stevioside and rebaudioside A, are natural, non-caloric sweet-tasting organic molecules, present in extracts of the scrub plant Stevia rebaudiana, which are widely used as sweeteners in consumer foods and beverages. TRPM5 is a Ca2+-activated cation channel expressed in type II taste receptor cells and pancreatic β-cells. Here we show that stevioside, rebaudioside A and their aglycon steviol potentiate the activity of TRPM5. We find that SGs potentiate perception of bitter, sweet and umami taste, and enhance glucose-induced insulin secretion in a Trpm5-dependent manner. Daily consumption of stevioside prevents development of high-fat-diet-induced diabetic hyperglycaemia in wild-type mice, but not in Trpm5-/- mice. These results elucidate a molecular mechanism of action of SGs and identify TRPM5 as a potential target to prevent and treat type 2 diabetes.

Original language	English
Pages (from-to)	14733
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms14733
Publication status	Published - 31 Mar 2017
Externally published	Yes

Keywords

Animals
Blood Glucose/drug effects
Diabetes Mellitus, Type 2/metabolism
Diet, High-Fat
Diterpenes, Kaurane/pharmacology
Female
Glucosides/pharmacology
HEK293 Cells
Humans
Insulin/metabolism
Insulin Secretion
Insulin-Secreting Cells/drug effects
Male
Mice
Mice, Knockout
Patch-Clamp Techniques
Sweetening Agents/pharmacology
TRPM Cation Channels/drug effects
Taste/drug effects

Access to Document

10.1038/ncomms14733Licence: CC BY

Cite this

Philippaert, K., Pironet, A., Mesuere, M., Sones, W., Vermeiren, L., Kerselaers, S., Pinto, S., Segal, A., Antoine, N., Gysemans, C., Laureys, J., Lemaire, K., Gilon, P., Cuypers, E., Tytgat, J., Mathieu, C., Schuit, F., Rorsman, P., Talavera, K., ... Vennekens, R. (2017). Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. Nature Communications, 8, 14733. https://doi.org/10.1038/ncomms14733

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title = "Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity",

abstract = "Steviol glycosides (SGs), such as stevioside and rebaudioside A, are natural, non-caloric sweet-tasting organic molecules, present in extracts of the scrub plant Stevia rebaudiana, which are widely used as sweeteners in consumer foods and beverages. TRPM5 is a Ca2+-activated cation channel expressed in type II taste receptor cells and pancreatic β-cells. Here we show that stevioside, rebaudioside A and their aglycon steviol potentiate the activity of TRPM5. We find that SGs potentiate perception of bitter, sweet and umami taste, and enhance glucose-induced insulin secretion in a Trpm5-dependent manner. Daily consumption of stevioside prevents development of high-fat-diet-induced diabetic hyperglycaemia in wild-type mice, but not in Trpm5-/- mice. These results elucidate a molecular mechanism of action of SGs and identify TRPM5 as a potential target to prevent and treat type 2 diabetes.",

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author = "Koenraad Philippaert and Andy Pironet and Margot Mesuere and William Sones and Laura Vermeiren and Sara Kerselaers and S{\'i}lvia Pinto and Andrei Segal and Nancy Antoine and Conny Gysemans and Jos Laureys and Katleen Lemaire and Patrick Gilon and Eva Cuypers and Jan Tytgat and Chantal Mathieu and Frans Schuit and Patrik Rorsman and Karel Talavera and Thomas Voets and Rudi Vennekens",

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Philippaert, K, Pironet, A, Mesuere, M, Sones, W, Vermeiren, L, Kerselaers, S, Pinto, S, Segal, A, Antoine, N, Gysemans, C, Laureys, J, Lemaire, K, Gilon, P, Cuypers, E, Tytgat, J, Mathieu, C, Schuit, F, Rorsman, P, Talavera, K, Voets, T & Vennekens, R 2017, 'Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity', Nature Communications, vol. 8, pp. 14733. https://doi.org/10.1038/ncomms14733

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AU - Philippaert, Koenraad

AU - Pironet, Andy

AU - Mesuere, Margot

AU - Sones, William

AU - Vermeiren, Laura

AU - Kerselaers, Sara

AU - Pinto, Sílvia

AU - Segal, Andrei

AU - Antoine, Nancy

AU - Gysemans, Conny

AU - Laureys, Jos

AU - Lemaire, Katleen

AU - Gilon, Patrick

AU - Cuypers, Eva

AU - Tytgat, Jan

AU - Mathieu, Chantal

AU - Schuit, Frans

AU - Rorsman, Patrik

AU - Talavera, Karel

AU - Voets, Thomas

AU - Vennekens, Rudi

PY - 2017/3/31

Y1 - 2017/3/31

N2 - Steviol glycosides (SGs), such as stevioside and rebaudioside A, are natural, non-caloric sweet-tasting organic molecules, present in extracts of the scrub plant Stevia rebaudiana, which are widely used as sweeteners in consumer foods and beverages. TRPM5 is a Ca2+-activated cation channel expressed in type II taste receptor cells and pancreatic β-cells. Here we show that stevioside, rebaudioside A and their aglycon steviol potentiate the activity of TRPM5. We find that SGs potentiate perception of bitter, sweet and umami taste, and enhance glucose-induced insulin secretion in a Trpm5-dependent manner. Daily consumption of stevioside prevents development of high-fat-diet-induced diabetic hyperglycaemia in wild-type mice, but not in Trpm5-/- mice. These results elucidate a molecular mechanism of action of SGs and identify TRPM5 as a potential target to prevent and treat type 2 diabetes.

AB - Steviol glycosides (SGs), such as stevioside and rebaudioside A, are natural, non-caloric sweet-tasting organic molecules, present in extracts of the scrub plant Stevia rebaudiana, which are widely used as sweeteners in consumer foods and beverages. TRPM5 is a Ca2+-activated cation channel expressed in type II taste receptor cells and pancreatic β-cells. Here we show that stevioside, rebaudioside A and their aglycon steviol potentiate the activity of TRPM5. We find that SGs potentiate perception of bitter, sweet and umami taste, and enhance glucose-induced insulin secretion in a Trpm5-dependent manner. Daily consumption of stevioside prevents development of high-fat-diet-induced diabetic hyperglycaemia in wild-type mice, but not in Trpm5-/- mice. These results elucidate a molecular mechanism of action of SGs and identify TRPM5 as a potential target to prevent and treat type 2 diabetes.

KW - Animals

KW - Blood Glucose/drug effects

KW - Diabetes Mellitus, Type 2/metabolism

KW - Diet, High-Fat

KW - Diterpenes, Kaurane/pharmacology

KW - Female

KW - Glucosides/pharmacology

KW - HEK293 Cells

KW - Humans

KW - Insulin/metabolism

KW - Insulin Secretion

KW - Insulin-Secreting Cells/drug effects

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Patch-Clamp Techniques

KW - Sweetening Agents/pharmacology

KW - TRPM Cation Channels/drug effects

KW - Taste/drug effects

U2 - 10.1038/ncomms14733

DO - 10.1038/ncomms14733

M3 - Article

C2 - 28361903

SN - 2041-1723

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SP - 14733

JO - Nature Communications

JF - Nature Communications

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