The noncaloric sweetener rebaudioside a stimulates glucagon-like peptide 1 release and increases enteroendocrine cell numbers in 2-dimensional mouse organoids derived from different locations of the intestine

Nikkie van der Wielen, Jean Paul ten Klooster, Susanne Muckenschnabl, Raymond Pieters, Henk F.J. Hendriks, Renger F. Witkamp, Jocelijn Meijerink

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)

Abstract

Background: Glucagon-like peptide 1 (GLP-1) contributes to satiety and plays a pivotal role in insulin secretion and glucose homeostasis. Similar to GLP-1, peptide YY (PYY) and cholecystokinin also influence food intake. The secretion of these hormones by enteroendocrine cells along the intestine is modulated by nutrients. Preparations from the Stevia rebaudiana plant, including rebaudioside A, are increasingly being used as noncaloric sweeteners. Objective: We investigated the effects of rebaudioside A on enteroendocrine cells by assessing both cell numbers as well as their secretory capacity in an organoid model. Methods: A 2-dimensional organoid model derived from duodenal, jejunal, and ileal crypts of a C57BL/6J mouse was developed and characterized with the use of gene expression and immunofluorescence. We stimulated these organoids with 10 mmol/L rebaudioside A for 1 h and measured their GLP-1, PYY, and cholecystokinin release. We also analyzed the effects of rebaudioside A on gene expression in enteroendocrine cells after an 18-h incubation. Results: The 2-dimensional organoids contained crypt cells and differentiated villus cells, including enterocytes and goblet and enteroendocrine cells. These enteroendocrine cells stained positive for GLP-1, PYY, and serotonin. The cultured 2-dimensional organoids maintained their location-specific gene expression patterns. Compared with the control, rebaudioside A induced GLP-1 secretion 1.7-fold in the duodenum (P <0.01), 2.2-fold in the jejunum (P <0.01), and 4.3-fold in the ileum (P <0.001). PYY release was increased by rebaudioside A 3-fold in the ileumcompared with the control (P <0.05). Long-term (18-h) stimulation with the sweetener induced the expression of the enteroendocrine-specific markers chromogranin A, glucagon, Pyy, and cholecystokinin 3.5- (P <0.001), 3.5- (P <0.001), 3.8- (P <0.05), and 6.5-fold (P <0.001), respectively. Conclusions: These results show novel ex vivo effects of rebaudioside A on enteroendocrine cells of the mouse small intestine and highlight potentially new applications for rebaudioside A in metabolic diseases.

LanguageEnglish
Pages2429-2435
JournalThe Journal of Nutrition
Volume146
Issue number12
DOIs
Publication statusPublished - 2016

Fingerprint

Organoids
Enteroendocrine Cells
Sweetening Agents
Glucagon-Like Peptide 1
Intestines
Cell Count
Peptide YY
Cholecystokinin
Gene Expression
Stevia
Chromogranin A
Goblet Cells
rebaudioside A
Enterocytes
Metabolic Diseases
Jejunum
Glucagon
Inbred C57BL Mouse
Ileum
Duodenum

Keywords

  • Duodenum
  • GLP-1
  • Glucagon-like peptide 1
  • Gut hormone
  • Ileum
  • Jejunum
  • Minigut
  • Organoids
  • Peptide YY
  • Stevia

Cite this

@article{d89e168805264d57b504c7512e9bf37c,
title = "The noncaloric sweetener rebaudioside a stimulates glucagon-like peptide 1 release and increases enteroendocrine cell numbers in 2-dimensional mouse organoids derived from different locations of the intestine",
abstract = "Background: Glucagon-like peptide 1 (GLP-1) contributes to satiety and plays a pivotal role in insulin secretion and glucose homeostasis. Similar to GLP-1, peptide YY (PYY) and cholecystokinin also influence food intake. The secretion of these hormones by enteroendocrine cells along the intestine is modulated by nutrients. Preparations from the Stevia rebaudiana plant, including rebaudioside A, are increasingly being used as noncaloric sweeteners. Objective: We investigated the effects of rebaudioside A on enteroendocrine cells by assessing both cell numbers as well as their secretory capacity in an organoid model. Methods: A 2-dimensional organoid model derived from duodenal, jejunal, and ileal crypts of a C57BL/6J mouse was developed and characterized with the use of gene expression and immunofluorescence. We stimulated these organoids with 10 mmol/L rebaudioside A for 1 h and measured their GLP-1, PYY, and cholecystokinin release. We also analyzed the effects of rebaudioside A on gene expression in enteroendocrine cells after an 18-h incubation. Results: The 2-dimensional organoids contained crypt cells and differentiated villus cells, including enterocytes and goblet and enteroendocrine cells. These enteroendocrine cells stained positive for GLP-1, PYY, and serotonin. The cultured 2-dimensional organoids maintained their location-specific gene expression patterns. Compared with the control, rebaudioside A induced GLP-1 secretion 1.7-fold in the duodenum (P <0.01), 2.2-fold in the jejunum (P <0.01), and 4.3-fold in the ileum (P <0.001). PYY release was increased by rebaudioside A 3-fold in the ileumcompared with the control (P <0.05). Long-term (18-h) stimulation with the sweetener induced the expression of the enteroendocrine-specific markers chromogranin A, glucagon, Pyy, and cholecystokinin 3.5- (P <0.001), 3.5- (P <0.001), 3.8- (P <0.05), and 6.5-fold (P <0.001), respectively. Conclusions: These results show novel ex vivo effects of rebaudioside A on enteroendocrine cells of the mouse small intestine and highlight potentially new applications for rebaudioside A in metabolic diseases.",
keywords = "Duodenum, GLP-1, Glucagon-like peptide 1, Gut hormone, Ileum, Jejunum, Minigut, Organoids, Peptide YY, Stevia",
author = "{van der Wielen}, Nikkie and {ten Klooster}, {Jean Paul} and Susanne Muckenschnabl and Raymond Pieters and Hendriks, {Henk F.J.} and Witkamp, {Renger F.} and Jocelijn Meijerink",
year = "2016",
doi = "10.3945/jn.116.232678",
language = "English",
volume = "146",
pages = "2429--2435",
journal = "The Journal of Nutrition",
issn = "0022-3166",
publisher = "American Society for Nutrition",
number = "12",

}

The noncaloric sweetener rebaudioside a stimulates glucagon-like peptide 1 release and increases enteroendocrine cell numbers in 2-dimensional mouse organoids derived from different locations of the intestine. / van der Wielen, Nikkie; ten Klooster, Jean Paul; Muckenschnabl, Susanne; Pieters, Raymond; Hendriks, Henk F.J.; Witkamp, Renger F.; Meijerink, Jocelijn.

In: The Journal of Nutrition, Vol. 146, No. 12, 2016, p. 2429-2435.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The noncaloric sweetener rebaudioside a stimulates glucagon-like peptide 1 release and increases enteroendocrine cell numbers in 2-dimensional mouse organoids derived from different locations of the intestine

AU - van der Wielen, Nikkie

AU - ten Klooster, Jean Paul

AU - Muckenschnabl, Susanne

AU - Pieters, Raymond

AU - Hendriks, Henk F.J.

AU - Witkamp, Renger F.

AU - Meijerink, Jocelijn

PY - 2016

Y1 - 2016

N2 - Background: Glucagon-like peptide 1 (GLP-1) contributes to satiety and plays a pivotal role in insulin secretion and glucose homeostasis. Similar to GLP-1, peptide YY (PYY) and cholecystokinin also influence food intake. The secretion of these hormones by enteroendocrine cells along the intestine is modulated by nutrients. Preparations from the Stevia rebaudiana plant, including rebaudioside A, are increasingly being used as noncaloric sweeteners. Objective: We investigated the effects of rebaudioside A on enteroendocrine cells by assessing both cell numbers as well as their secretory capacity in an organoid model. Methods: A 2-dimensional organoid model derived from duodenal, jejunal, and ileal crypts of a C57BL/6J mouse was developed and characterized with the use of gene expression and immunofluorescence. We stimulated these organoids with 10 mmol/L rebaudioside A for 1 h and measured their GLP-1, PYY, and cholecystokinin release. We also analyzed the effects of rebaudioside A on gene expression in enteroendocrine cells after an 18-h incubation. Results: The 2-dimensional organoids contained crypt cells and differentiated villus cells, including enterocytes and goblet and enteroendocrine cells. These enteroendocrine cells stained positive for GLP-1, PYY, and serotonin. The cultured 2-dimensional organoids maintained their location-specific gene expression patterns. Compared with the control, rebaudioside A induced GLP-1 secretion 1.7-fold in the duodenum (P <0.01), 2.2-fold in the jejunum (P <0.01), and 4.3-fold in the ileum (P <0.001). PYY release was increased by rebaudioside A 3-fold in the ileumcompared with the control (P <0.05). Long-term (18-h) stimulation with the sweetener induced the expression of the enteroendocrine-specific markers chromogranin A, glucagon, Pyy, and cholecystokinin 3.5- (P <0.001), 3.5- (P <0.001), 3.8- (P <0.05), and 6.5-fold (P <0.001), respectively. Conclusions: These results show novel ex vivo effects of rebaudioside A on enteroendocrine cells of the mouse small intestine and highlight potentially new applications for rebaudioside A in metabolic diseases.

AB - Background: Glucagon-like peptide 1 (GLP-1) contributes to satiety and plays a pivotal role in insulin secretion and glucose homeostasis. Similar to GLP-1, peptide YY (PYY) and cholecystokinin also influence food intake. The secretion of these hormones by enteroendocrine cells along the intestine is modulated by nutrients. Preparations from the Stevia rebaudiana plant, including rebaudioside A, are increasingly being used as noncaloric sweeteners. Objective: We investigated the effects of rebaudioside A on enteroendocrine cells by assessing both cell numbers as well as their secretory capacity in an organoid model. Methods: A 2-dimensional organoid model derived from duodenal, jejunal, and ileal crypts of a C57BL/6J mouse was developed and characterized with the use of gene expression and immunofluorescence. We stimulated these organoids with 10 mmol/L rebaudioside A for 1 h and measured their GLP-1, PYY, and cholecystokinin release. We also analyzed the effects of rebaudioside A on gene expression in enteroendocrine cells after an 18-h incubation. Results: The 2-dimensional organoids contained crypt cells and differentiated villus cells, including enterocytes and goblet and enteroendocrine cells. These enteroendocrine cells stained positive for GLP-1, PYY, and serotonin. The cultured 2-dimensional organoids maintained their location-specific gene expression patterns. Compared with the control, rebaudioside A induced GLP-1 secretion 1.7-fold in the duodenum (P <0.01), 2.2-fold in the jejunum (P <0.01), and 4.3-fold in the ileum (P <0.001). PYY release was increased by rebaudioside A 3-fold in the ileumcompared with the control (P <0.05). Long-term (18-h) stimulation with the sweetener induced the expression of the enteroendocrine-specific markers chromogranin A, glucagon, Pyy, and cholecystokinin 3.5- (P <0.001), 3.5- (P <0.001), 3.8- (P <0.05), and 6.5-fold (P <0.001), respectively. Conclusions: These results show novel ex vivo effects of rebaudioside A on enteroendocrine cells of the mouse small intestine and highlight potentially new applications for rebaudioside A in metabolic diseases.

KW - Duodenum

KW - GLP-1

KW - Glucagon-like peptide 1

KW - Gut hormone

KW - Ileum

KW - Jejunum

KW - Minigut

KW - Organoids

KW - Peptide YY

KW - Stevia

U2 - 10.3945/jn.116.232678

DO - 10.3945/jn.116.232678

M3 - Article

VL - 146

SP - 2429

EP - 2435

JO - The Journal of Nutrition

T2 - The Journal of Nutrition

JF - The Journal of Nutrition

SN - 0022-3166

IS - 12

ER -