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.
authors.affiliation: Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.|TRP Research Platform Leuven (TRPLe), KU Leuven, Herestraat 49/802, 3000 Leuven, Belgium.
authors.forename: Koenraad
authors.identifier: 0000-0002-5861-2275
authors.initials: K
authors.lastname: Philippaert
authors.affiliation: Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.|TRP Research Platform Leuven (TRPLe), KU Leuven, Herestraat 49/802, 3000 Leuven, Belgium.
authors.forename: Andy
authors.initials: A
authors.lastname: Pironet
authors.affiliation: Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.|TRP Research Platform Leuven (TRPLe), KU Leuven, Herestraat 49/802, 3000 Leuven, Belgium.
authors.forename: Margot
authors.initials: M
authors.lastname: Mesuere
authors.affiliation: Oxford Centre for Diabetes, Radcliffe Department of Medicine, Endocrinology and Metabolism, Churchill Hospital, Old Road, Oxford OX3 7LE, UK.
authors.forename: William
authors.initials: W
authors.lastname: Sones
authors.affiliation: Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.|TRP Research Platform Leuven (TRPLe), KU Leuven, Herestraat 49/802, 3000 Leuven, Belgium.
authors.forename: Laura
authors.initials: L
authors.lastname: Vermeiren
authors.affiliation: Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.|TRP Research Platform Leuven (TRPLe), KU Leuven, Herestraat 49/802, 3000 Leuven, Belgium.
authors.forename: Sara
authors.initials: S
authors.lastname: Kerselaers
authors.affiliation: Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.|TRP Research Platform Leuven (TRPLe), KU Leuven, Herestraat 49/802, 3000 Leuven, Belgium.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Pinto
authors.affiliation: Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.|TRP Research Platform Leuven (TRPLe), KU Leuven, Herestraat 49/802, 3000 Leuven, Belgium.
authors.forename: Andrei
authors.initials: A
authors.lastname: Segal
authors.affiliation: Pôle d'endocrinologie, diabète et nutrition, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, 1200 Brussels, Belgium.
authors.forename: Nancy
authors.initials: N
authors.lastname: Antoine
authors.affiliation: Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Conny
authors.initials: C
authors.lastname: Gysemans
authors.affiliation: Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Jos
authors.initials: J
authors.lastname: Laureys
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Katleen
authors.initials: K
authors.lastname: Lemaire
authors.affiliation: Pôle d'endocrinologie, diabète et nutrition, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, 1200 Brussels, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gilon
authors.affiliation: Toxicology and Pharmacology, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Cuypers
authors.affiliation: Toxicology and Pharmacology, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
authors.affiliation: Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.affiliation: Oxford Centre for Diabetes, Radcliffe Department of Medicine, Endocrinology and Metabolism, Churchill Hospital, Old Road, Oxford OX3 7LE, UK.
authors.forename: Patrik
authors.initials: P
authors.lastname: Rorsman
authors.affiliation: Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.|TRP Research Platform Leuven (TRPLe), KU Leuven, Herestraat 49/802, 3000 Leuven, Belgium.
authors.forename: Karel
authors.initials: K
authors.lastname: Talavera
authors.affiliation: Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.|TRP Research Platform Leuven (TRPLe), KU Leuven, Herestraat 49/802, 3000 Leuven, Belgium.
authors.forename: Thomas
authors.identifier: 0000-0001-5526-5821
authors.initials: T
authors.lastname: Voets
authors.affiliation: Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.|TRP Research Platform Leuven (TRPLe), KU Leuven, Herestraat 49/802, 3000 Leuven, Belgium.
authors.forename: Rudi
authors.identifier: 0000-0002-2564-5150
authors.initials: R
authors.lastname: Vennekens
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D059305:Diet, High-Fat; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D013549:Sweetening Agents / Q000494:pharmacology*; D050053:TRPM Cation Channels / Q000187:drug effects* / Q000378:metabolism; D013649:Taste / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D045786:Diterpenes, Kaurane; D005960:Glucosides; D007328:Insulin; D013549:Sweetening Agents; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; C404409:TRPM5 protein, human; C498617:Trpm5 protein, mouse; C012043:stevioside; C012042:steviol; C025474:rebaudioside A