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Glutamine Triggers and Potentiates Glucagon-Like Peptide-1 Secretion by Raising Cytosolic Ca(2+) and cAMP
L-glutamine stimulates glucagon-like peptide 1 (GLP-1) secretion in human subjects and cell lines. As recent advances have enabled the study of primary GLP-1–releasing L cells, this study aimed to characterize glutamine-sensing pathways in native murine L cells. L cells were identified using transge...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Endocrine Society
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140224/ https://www.ncbi.nlm.nih.gov/pubmed/21209017 http://dx.doi.org/10.1210/en.2010-0956 |
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author | Tolhurst, Gwen Zheng, Yue Parker, Helen E. Habib, Abdella M. Reimann, Frank Gribble, Fiona M. |
author_facet | Tolhurst, Gwen Zheng, Yue Parker, Helen E. Habib, Abdella M. Reimann, Frank Gribble, Fiona M. |
author_sort | Tolhurst, Gwen |
collection | PubMed |
description | L-glutamine stimulates glucagon-like peptide 1 (GLP-1) secretion in human subjects and cell lines. As recent advances have enabled the study of primary GLP-1–releasing L cells, this study aimed to characterize glutamine-sensing pathways in native murine L cells. L cells were identified using transgenic mice with cell-specific expression of fluorescent markers. Cells were studied in primary colonic cultures from adult mice, or purified by flow cytometry for expression analysis. Intracellular Ca(2+) was monitored in cultures loaded with Fura2, and cAMP was studied using Förster resonance energy transfer sensors expressed in GLUTag cells. Asparagine, phenylalanine, and glutamine (10 mm) triggered GLP-1 release from primary cultures, but glutamine was the most efficacious, increasing secretion 1.9-fold with an EC(50) of 0.19 mm. Several amino acids triggered Ca(2+) changes in L cells, comparable in magnitude to that induced by glutamine. Glutamine-induced Ca(2+) responses were abolished in low Na(+) solution and attenuated in Ca(2+) free solution, suggesting a role for Na(+) dependent uptake and Ca(2+) influx. The greater effectiveness of glutamine as a secretagogue was paralleled by its ability to increase cAMP in GLUTag cells. Glutamine elevated intracellular cAMP to 36% of that produced by a maximal stimulus, whereas asparagine only increased intracellular cAMP by 24% and phenylalanine was without effect. Glutamine elevates both cytosolic Ca(2+) and cAMP in L cells, which may account for the effectiveness of glutamine as a GLP-1 secretagogue. Therapeutic agents like glutamine that target synergistic pathways in L cells might play a future role in the treatment of type 2 diabetes. |
format | Online Article Text |
id | pubmed-3140224 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Endocrine Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-31402242011-07-20 Glutamine Triggers and Potentiates Glucagon-Like Peptide-1 Secretion by Raising Cytosolic Ca(2+) and cAMP Tolhurst, Gwen Zheng, Yue Parker, Helen E. Habib, Abdella M. Reimann, Frank Gribble, Fiona M. Endocrinology Diabetes-Insulin-Glucagon-Gastrointestinal L-glutamine stimulates glucagon-like peptide 1 (GLP-1) secretion in human subjects and cell lines. As recent advances have enabled the study of primary GLP-1–releasing L cells, this study aimed to characterize glutamine-sensing pathways in native murine L cells. L cells were identified using transgenic mice with cell-specific expression of fluorescent markers. Cells were studied in primary colonic cultures from adult mice, or purified by flow cytometry for expression analysis. Intracellular Ca(2+) was monitored in cultures loaded with Fura2, and cAMP was studied using Förster resonance energy transfer sensors expressed in GLUTag cells. Asparagine, phenylalanine, and glutamine (10 mm) triggered GLP-1 release from primary cultures, but glutamine was the most efficacious, increasing secretion 1.9-fold with an EC(50) of 0.19 mm. Several amino acids triggered Ca(2+) changes in L cells, comparable in magnitude to that induced by glutamine. Glutamine-induced Ca(2+) responses were abolished in low Na(+) solution and attenuated in Ca(2+) free solution, suggesting a role for Na(+) dependent uptake and Ca(2+) influx. The greater effectiveness of glutamine as a secretagogue was paralleled by its ability to increase cAMP in GLUTag cells. Glutamine elevated intracellular cAMP to 36% of that produced by a maximal stimulus, whereas asparagine only increased intracellular cAMP by 24% and phenylalanine was without effect. Glutamine elevates both cytosolic Ca(2+) and cAMP in L cells, which may account for the effectiveness of glutamine as a GLP-1 secretagogue. Therapeutic agents like glutamine that target synergistic pathways in L cells might play a future role in the treatment of type 2 diabetes. Endocrine Society 2011-02 2011-01-05 /pmc/articles/PMC3140224/ /pubmed/21209017 http://dx.doi.org/10.1210/en.2010-0956 Text en Copyright © 2011 by The Endocrine Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/us/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Diabetes-Insulin-Glucagon-Gastrointestinal Tolhurst, Gwen Zheng, Yue Parker, Helen E. Habib, Abdella M. Reimann, Frank Gribble, Fiona M. Glutamine Triggers and Potentiates Glucagon-Like Peptide-1 Secretion by Raising Cytosolic Ca(2+) and cAMP |
title | Glutamine Triggers and Potentiates Glucagon-Like Peptide-1 Secretion by Raising Cytosolic Ca(2+) and cAMP |
title_full | Glutamine Triggers and Potentiates Glucagon-Like Peptide-1 Secretion by Raising Cytosolic Ca(2+) and cAMP |
title_fullStr | Glutamine Triggers and Potentiates Glucagon-Like Peptide-1 Secretion by Raising Cytosolic Ca(2+) and cAMP |
title_full_unstemmed | Glutamine Triggers and Potentiates Glucagon-Like Peptide-1 Secretion by Raising Cytosolic Ca(2+) and cAMP |
title_short | Glutamine Triggers and Potentiates Glucagon-Like Peptide-1 Secretion by Raising Cytosolic Ca(2+) and cAMP |
title_sort | glutamine triggers and potentiates glucagon-like peptide-1 secretion by raising cytosolic ca(2+) and camp |
topic | Diabetes-Insulin-Glucagon-Gastrointestinal |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140224/ https://www.ncbi.nlm.nih.gov/pubmed/21209017 http://dx.doi.org/10.1210/en.2010-0956 |
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