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Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells

Glucagon like peptide 1 (GLP-1) based therapies are now widely used for the treatment of type 2 diabetes. Developing our understanding of intestinal GLP-1 release may facilitate the development of new therapeutics aimed at targeting the GLP-1 producing L-cells. This study was undertaken to character...

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Autores principales: Rogers, G J, Tolhurst, G, Ramzan, A, Habib, A M, Parker, H E, Gribble, F M, Reimann, F
Formato: Texto
Lenguaje:English
Publicado: Blackwell Science Inc 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060588/
https://www.ncbi.nlm.nih.gov/pubmed/21224236
http://dx.doi.org/10.1113/jphysiol.2010.198069
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author Rogers, G J
Tolhurst, G
Ramzan, A
Habib, A M
Parker, H E
Gribble, F M
Reimann, F
author_facet Rogers, G J
Tolhurst, G
Ramzan, A
Habib, A M
Parker, H E
Gribble, F M
Reimann, F
author_sort Rogers, G J
collection PubMed
description Glucagon like peptide 1 (GLP-1) based therapies are now widely used for the treatment of type 2 diabetes. Developing our understanding of intestinal GLP-1 release may facilitate the development of new therapeutics aimed at targeting the GLP-1 producing L-cells. This study was undertaken to characterise the electrical activity of primary L-cells and the importance of voltage gated sodium and calcium channels for GLP-1 secretion. Primary murine L-cells were identified and purified using transgenic mice expressing a fluorescent protein driven by the proglucagon promoter. Fluorescent L-cells were identified within primary colonic cultures for patch clamp recordings. GLP-1 secretion was measured from primary colonic cultures. L-cells purified by flow cytometry were used to measure gene expression by microarray and quantitative RT-PCR. Electrical activity in L-cells was due to large voltage gated sodium currents, inhibition of which by tetrodotoxin reduced both basal and glutamine-stimulated GLP-1 secretion. Voltage gated calcium channels were predominantly of the L-type, Q-type and T-type, by expression analysis, consistent with the finding that GLP-1 release was blocked both by nifedipine and ω-conotoxin MVIIC. We observed large voltage-dependent potassium currents, but only a small chromanol sensitive current that might be attributable to KCNQ1. GLP-1 release from primary L-cells is linked to electrical activity and activation of L-type and Q-type calcium currents. The concept of an electrically excitable L-cell provides a basis for understanding how GLP-1 release may be modulated by nutrient, hormonal and pharmaceutical stimuli.
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spelling pubmed-30605882012-03-01 Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells Rogers, G J Tolhurst, G Ramzan, A Habib, A M Parker, H E Gribble, F M Reimann, F J Physiol Molecular and Cellular Glucagon like peptide 1 (GLP-1) based therapies are now widely used for the treatment of type 2 diabetes. Developing our understanding of intestinal GLP-1 release may facilitate the development of new therapeutics aimed at targeting the GLP-1 producing L-cells. This study was undertaken to characterise the electrical activity of primary L-cells and the importance of voltage gated sodium and calcium channels for GLP-1 secretion. Primary murine L-cells were identified and purified using transgenic mice expressing a fluorescent protein driven by the proglucagon promoter. Fluorescent L-cells were identified within primary colonic cultures for patch clamp recordings. GLP-1 secretion was measured from primary colonic cultures. L-cells purified by flow cytometry were used to measure gene expression by microarray and quantitative RT-PCR. Electrical activity in L-cells was due to large voltage gated sodium currents, inhibition of which by tetrodotoxin reduced both basal and glutamine-stimulated GLP-1 secretion. Voltage gated calcium channels were predominantly of the L-type, Q-type and T-type, by expression analysis, consistent with the finding that GLP-1 release was blocked both by nifedipine and ω-conotoxin MVIIC. We observed large voltage-dependent potassium currents, but only a small chromanol sensitive current that might be attributable to KCNQ1. GLP-1 release from primary L-cells is linked to electrical activity and activation of L-type and Q-type calcium currents. The concept of an electrically excitable L-cell provides a basis for understanding how GLP-1 release may be modulated by nutrient, hormonal and pharmaceutical stimuli. Blackwell Science Inc 2011-03-01 2011-01-04 /pmc/articles/PMC3060588/ /pubmed/21224236 http://dx.doi.org/10.1113/jphysiol.2010.198069 Text en Journal compilation © 2011 The Physiological Society
spellingShingle Molecular and Cellular
Rogers, G J
Tolhurst, G
Ramzan, A
Habib, A M
Parker, H E
Gribble, F M
Reimann, F
Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells
title Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells
title_full Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells
title_fullStr Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells
title_full_unstemmed Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells
title_short Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells
title_sort electrical activity-triggered glucagon-like peptide-1 secretion from primary murine l-cells
topic Molecular and Cellular
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060588/
https://www.ncbi.nlm.nih.gov/pubmed/21224236
http://dx.doi.org/10.1113/jphysiol.2010.198069
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