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

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

doi:10.1038/ncomms14733

Cited by 146 publications

(130 citation statements)

References 47 publications

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“…In addition, as our data showed that a TRPM5 inhibitor can alleviate behavioral bitter aversion in chickens, this suggests the possibility of modifying chickens' taste perceptions to feed ingredients by a TRPM5 activator such as steviol glycosides (Philippaert et al 2017) or an inhibitor. In addition, as our data showed that a TRPM5 inhibitor can alleviate behavioral bitter aversion in chickens, this suggests the possibility of modifying chickens' taste perceptions to feed ingredients by a TRPM5 activator such as steviol glycosides (Philippaert et al 2017) or an inhibitor.…”

Section: Resultsmentioning

confidence: 71%

“…We also observed that TRPM5 is involved in chickens' taste transduction, and this finding implies the possibility that chickens have thermal sensitivity of taste perception, and that the temperature of feeds affects taste perception of chickens. In addition, as our data showed that a TRPM5 inhibitor can alleviate behavioral bitter aversion in chickens, this suggests the possibility of modifying chickens' taste perceptions to feed ingredients by a TRPM5 activator such as steviol glycosides (Philippaert et al 2017) or an inhibitor. Figure 3 (A-C) The chicks' intakes of quinine hydrochloride (QHCl) solution were significantly decreased from 1.0 mmol/L compared to water, and their intakes of diphenidol hydrochloride (DHCl) solution were significantly decreased from 0.5 mmol/L.…”

Section: Resultsmentioning

confidence: 71%

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Expression levels of taste‐related genes in palate and tongue tip, and involvement of transient receptor potential subfamily M member 5 (TRPM5) in taste sense in chickens

Yoshida

Kawabata

et al. 2017

Animal Science Journal

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The elucidation of the mechanisms underlying the taste sense of chickens will contribute to improvements in poultry feeding, because the molecular mechanism of chickens' taste sense defines the feeding behavior of chickens. Here we focused on the gene expressions in two different oral tissues of chickens - the palate, which contains many taste buds, and the tongue tip, which contains few taste buds. Using the quantitative real-time polymerase chain reaction method, we found that the molecular markers for taste buds of chickens, that is α-gustducin and vimentin, were expressed significantly highly in the palate compared to the tongue tip. Our analyses also revealed that transient receptor potential subfamily M member 5 (TRPM5), a cation channel involved in taste transduction in mammals, was also highly expressed in the palate compared to the tongue tip. Our findings demonstrated that the expression patterns of these genes were significantly correlated. We showed that the aversion to bitter solution was alleviated by a TRPM5 inhibitor in behavior of chickens. Taken together, our findings enabled us to develop a simple method for screening taste-related genes in chickens. The use of this method demonstrated that TRPM5 was involved in chickens' taste transduction, and that a TRPM5 inhibitor can alleviate chickens' bitter taste perception of feed ingredients.

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Section: Resultsmentioning

confidence: 71%

Section: Resultsmentioning

confidence: 71%

Expression levels of taste‐related genes in palate and tongue tip, and involvement of transient receptor potential subfamily M member 5 (TRPM5) in taste sense in chickens

Yoshida

Kawabata

et al. 2017

Animal Science Journal

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“…TRPM5 is a Ca 2+ -dependent cation channel expressed in both type II taste receptor cells and pancreatic β-cells. 5 In the current study, we ex- histocompatibility (MHC) class I molecule has been found to be positively correlated with diabetes duration. 33 In addition, Pavlovic et al found elevated glucose levels to increase MHC class I mRNA levels twofold in both rat and human islet cell preparations, suggesting that a hyperglycaemic state is able to increase expression in islet β-cells.…”

Section: Effects Of 72-h Exposure To Svg On Gene Transcription In Mmentioning

confidence: 77%

“…Besides the sweet property, steviol glycosides also possess potential therapeutic benefits. A multitude of preclinical and clinical studies have demonstrated their antihyperglycaemic effects, including lowering postprandial blood glucose, 3,4 enhancing insulin secretion [5][6][7][8][9][10][11] and improving insulin sensitivity. 12,13 Steviol glycosides share steviol (ent-13-hydroxykaur-16-en-18oic acid) as the aglycone core structure and only differ in the number and type of sugar molecules attached (at R1 and R2), see Figure 1A Moreover, all steviol glycosides found in stevia leaf extracts share the same metabolic pathway.…”

Section: Introductionmentioning

confidence: 99%

Steviol glucuronide, a metabolite of steviol glycosides, potently stimulates insulin secretion from isolated mouse islets: Studies in vitro

Rebsdorf

Anker

et al. 2019

Endocrino Diabet & Metabol

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Aims Steviol glycosides are the sweet components extracted from medicinal plant Stevia rebaudiana Bertoni, which have antihyperglycaemic effects. Steviol glucuronide (SVG) is the metabolite excreted in human urine after oral administration of steviol glycosides. We aimed to clarify whether SVG exerts direct insulin stimulation from pancreatic islets and to explore its mode of action. Materials and Methods Insulin secretion was measured after 60 minutes static incubation of isolated mouse islets with (a) 10−9‐10−5 mol/L SVG at 16.7 mmol/L glucose and (b) 10−7 mol/L SVG at 3.3‐16.7 mmol/L glucose. Islets were perifused with 3.3 or 16.7 mmol/L glucose in the presence or absence of 10−7 mol/L SVG. Gene transcription was measured after 72 hours incubation in the presence or absence of 10−7 mol/L SVG. Results SVG dose‐dependently increased insulin secretion from mouse islets with 10−7 mol/L exerting the maximum effect in the presence of 16.7 mmol/L glucose (P < .001). The insulinotropic effect of SVG was critically dependent on the prevailing glucose concentration, and SVG (10−7 mol/L) enhanced insulin secretion at or above 11.1 mmol/L glucose (P < .001) and showed no effect at lower glucose concentrations. During perifusion of islets, SVG (10−7 mol/L) had a long‐acting and apparently reversible insulinotropic effect in the presence of 16.7 mmol/L glucose (P < .05). Gene‐transcript levels of B2m and Gcgr were markedly altered. Conclusion This is the first report to demonstrate that SVG stimulates insulin secretion in a dose‐ and glucose‐dependent manner from isolated mouse islets of Langerhans. SVG may be the main active metabolite after oral intake of steviol glycosides.

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“…In addition, one of the downstream signaling molecules of taste receptors, TRPM5, a Ca 2+ -activated cation channel, has been reported to localize in pancreatic β-cells. 40,41 Therefore, to elucidate the role of NNAT, it may be necessary to clarify the signaling pathways involved in keratinization in the filiform papillae of the tongue and the IRS in the hair follicle, in acrosome formation in the spermatozoa, in photoreception in the rod photoreceptors, and in characteristic signals in NNAT-positive stem/progenitor cells.…”

Section: Discussionmentioning

confidence: 99%

Characteristic Localization of Neuronatin in Rat Tissues

Kanno

Yoshida

Katō

et al. 2018

Preprint

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1 Neuronatin (Nnat) is expressed in the pituitary, pancreas, and other tissues; however, the 2 function of NNAT is still unclear. Recent studies have demonstrated that NNAT is 3 localized in the sex determining region Y-box 2-positive stem/progenitor cells in the 4 developing rat pituitary primordium and is downregulated during differentiation into 5 mature hormone-producing cells. Moreover, NNAT is widely localized in subcellular 6 organelles, excluding the Golgi. Here, we further evaluated NNAT expression and 7 intracellular localization in embryonic and postnatal rat tissues such as the pancreas, 8 tongue, whisker hair follicle, and testis. Immunohistochemistry showed that NNAT was 9 localized in undifferentiated cells (i.e., epithelial basal cells and basement cells in the 1 0 papillae of the tongue and round and elongated spermatids of the testis) as well as in 1 1 differentiated cells (insulin-positive cells and exocrine cells of the pancreas, taste 1 2 receptor cells of the fungiform papilla, the inner root sheath of whisker hair follicles, 1 3 and spermatozoa). Additionally, NNAT showed novel intracellular localization in 1 4 acrosomes in the spermatozoa. Because the endoplasmic reticulum (ER) is excluded 1 5from spermatozoa and sarco/ER Ca 2+ -ATPase isoform 2 (SERCA2) is absent from the 1 6 inner root sheath, these findings suggested that NNAT localization in the ER and its 1 7 interaction with SERCA2 were cell-or tissue-specific properties.

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

Cited by 146 publications

References 47 publications

Expression levels of taste‐related genes in palate and tongue tip, and involvement of transient receptor potential subfamily M member 5 (TRPM5) in taste sense in chickens

Expression levels of taste‐related genes in palate and tongue tip, and involvement of transient receptor potential subfamily M member 5 (TRPM5) in taste sense in chickens

Steviol glucuronide, a metabolite of steviol glycosides, potently stimulates insulin secretion from isolated mouse islets: Studies in vitro

Characteristic Localization of Neuronatin in Rat Tissues

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