Cargando…
Serotonin-secreting enteroendocrine cells respond via diverse mechanisms to acute and chronic changes in glucose availability
BACKGROUND: Enteroendocrine cells collectively constitute our largest endocrine tissue, with serotonin (5-HT) secreting enterochromaffin (EC) cells being the largest component (~50 %). This gut-derived 5-HT has multiple paracrine and endocrine roles. EC cells are thought to act as nutrient sensors a...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678665/ https://www.ncbi.nlm.nih.gov/pubmed/26673561 http://dx.doi.org/10.1186/s12986-015-0051-0 |
_version_ | 1782405483724800000 |
---|---|
author | Zelkas, Leah Raghupathi, Ravi Lumsden, Amanda L. Martin, Alyce M. Sun, Emily Spencer, Nick J. Young, Richard L. Keating, Damien J. |
author_facet | Zelkas, Leah Raghupathi, Ravi Lumsden, Amanda L. Martin, Alyce M. Sun, Emily Spencer, Nick J. Young, Richard L. Keating, Damien J. |
author_sort | Zelkas, Leah |
collection | PubMed |
description | BACKGROUND: Enteroendocrine cells collectively constitute our largest endocrine tissue, with serotonin (5-HT) secreting enterochromaffin (EC) cells being the largest component (~50 %). This gut-derived 5-HT has multiple paracrine and endocrine roles. EC cells are thought to act as nutrient sensors and luminal glucose is the major absorbed form of carbohydrate in the gut and activates secretion in an array of cell types. It is unknown whether EC cells release 5-HT in response to glucose in primary EC cells. Furthermore, fasting augments 5-HT synthesis and release into the circulation. However, which nutrients cause fasting-induced synthesis of EC cell 5-HT is unknown. Here we examine the effects of acute and chronic changes in glucose availability on 5-HT release from intact tissue and single EC cells. METHODS: We utilised established approaches in our laboratories measuring 5-HT release in intact mouse colon with amperometry. We then examined single EC cells function using our published protocol in guinea-pig colon. Single cell Ca(2+) imaging and amperometry were used with these cells. Real-time PCR was used along with amperometry, on primary EC cells cultured for 24 h in 5 or 25 mM glucose. RESULTS: We demonstrate that acute increases in glucose, at levels found in the gut lumen rather than in plasma, trigger 5-HT release from intact colon, and cause Ca(2+) entry and 5-HT release in primary EC cells. Single cell amperometry demonstrates that high glucose increases the amount of 5-HT released from individual vesicles as they undergo exocytosis. Finally, 24 h incubation of EC cells in low glucose causes an increase in the transcription of the 5-HT synthesising enzyme Tph1 as well as increasing in 5-HT secretion in EC cells. CONCLUSIONS: We demonstrate that primary EC cells respond to acute changes in glucose availability through increases in intracellular Ca(2+) the activation of 5-HT secretion, but respond to chronic changes in glucose levels through the transcriptional regulation of Tph1 to alter 5-HT synthesis. |
format | Online Article Text |
id | pubmed-4678665 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46786652015-12-16 Serotonin-secreting enteroendocrine cells respond via diverse mechanisms to acute and chronic changes in glucose availability Zelkas, Leah Raghupathi, Ravi Lumsden, Amanda L. Martin, Alyce M. Sun, Emily Spencer, Nick J. Young, Richard L. Keating, Damien J. Nutr Metab (Lond) Research BACKGROUND: Enteroendocrine cells collectively constitute our largest endocrine tissue, with serotonin (5-HT) secreting enterochromaffin (EC) cells being the largest component (~50 %). This gut-derived 5-HT has multiple paracrine and endocrine roles. EC cells are thought to act as nutrient sensors and luminal glucose is the major absorbed form of carbohydrate in the gut and activates secretion in an array of cell types. It is unknown whether EC cells release 5-HT in response to glucose in primary EC cells. Furthermore, fasting augments 5-HT synthesis and release into the circulation. However, which nutrients cause fasting-induced synthesis of EC cell 5-HT is unknown. Here we examine the effects of acute and chronic changes in glucose availability on 5-HT release from intact tissue and single EC cells. METHODS: We utilised established approaches in our laboratories measuring 5-HT release in intact mouse colon with amperometry. We then examined single EC cells function using our published protocol in guinea-pig colon. Single cell Ca(2+) imaging and amperometry were used with these cells. Real-time PCR was used along with amperometry, on primary EC cells cultured for 24 h in 5 or 25 mM glucose. RESULTS: We demonstrate that acute increases in glucose, at levels found in the gut lumen rather than in plasma, trigger 5-HT release from intact colon, and cause Ca(2+) entry and 5-HT release in primary EC cells. Single cell amperometry demonstrates that high glucose increases the amount of 5-HT released from individual vesicles as they undergo exocytosis. Finally, 24 h incubation of EC cells in low glucose causes an increase in the transcription of the 5-HT synthesising enzyme Tph1 as well as increasing in 5-HT secretion in EC cells. CONCLUSIONS: We demonstrate that primary EC cells respond to acute changes in glucose availability through increases in intracellular Ca(2+) the activation of 5-HT secretion, but respond to chronic changes in glucose levels through the transcriptional regulation of Tph1 to alter 5-HT synthesis. BioMed Central 2015-12-15 /pmc/articles/PMC4678665/ /pubmed/26673561 http://dx.doi.org/10.1186/s12986-015-0051-0 Text en © Zelkas et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Zelkas, Leah Raghupathi, Ravi Lumsden, Amanda L. Martin, Alyce M. Sun, Emily Spencer, Nick J. Young, Richard L. Keating, Damien J. Serotonin-secreting enteroendocrine cells respond via diverse mechanisms to acute and chronic changes in glucose availability |
title | Serotonin-secreting enteroendocrine cells respond via diverse mechanisms to acute and chronic changes in glucose availability |
title_full | Serotonin-secreting enteroendocrine cells respond via diverse mechanisms to acute and chronic changes in glucose availability |
title_fullStr | Serotonin-secreting enteroendocrine cells respond via diverse mechanisms to acute and chronic changes in glucose availability |
title_full_unstemmed | Serotonin-secreting enteroendocrine cells respond via diverse mechanisms to acute and chronic changes in glucose availability |
title_short | Serotonin-secreting enteroendocrine cells respond via diverse mechanisms to acute and chronic changes in glucose availability |
title_sort | serotonin-secreting enteroendocrine cells respond via diverse mechanisms to acute and chronic changes in glucose availability |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678665/ https://www.ncbi.nlm.nih.gov/pubmed/26673561 http://dx.doi.org/10.1186/s12986-015-0051-0 |
work_keys_str_mv | AT zelkasleah serotoninsecretingenteroendocrinecellsrespondviadiversemechanismstoacuteandchronicchangesinglucoseavailability AT raghupathiravi serotoninsecretingenteroendocrinecellsrespondviadiversemechanismstoacuteandchronicchangesinglucoseavailability AT lumsdenamandal serotoninsecretingenteroendocrinecellsrespondviadiversemechanismstoacuteandchronicchangesinglucoseavailability AT martinalycem serotoninsecretingenteroendocrinecellsrespondviadiversemechanismstoacuteandchronicchangesinglucoseavailability AT sunemily serotoninsecretingenteroendocrinecellsrespondviadiversemechanismstoacuteandchronicchangesinglucoseavailability AT spencernickj serotoninsecretingenteroendocrinecellsrespondviadiversemechanismstoacuteandchronicchangesinglucoseavailability AT youngrichardl serotoninsecretingenteroendocrinecellsrespondviadiversemechanismstoacuteandchronicchangesinglucoseavailability AT keatingdamienj serotoninsecretingenteroendocrinecellsrespondviadiversemechanismstoacuteandchronicchangesinglucoseavailability |