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Glucose controls glucagon secretion by directly modulating cAMP in alpha cells
AIMS/HYPOTHESIS: Glucagon is critical for normal glucose homeostasis and aberrant secretion of the hormone aggravates dysregulated glucose control in diabetes. However, the mechanisms by which glucose controls glucagon secretion from pancreatic alpha cells remain elusive. The aim of this study was t...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560012/ https://www.ncbi.nlm.nih.gov/pubmed/30953108 http://dx.doi.org/10.1007/s00125-019-4857-6 |
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author | Yu, Qian Shuai, Hongyan Ahooghalandari, Parvin Gylfe, Erik Tengholm, Anders |
author_facet | Yu, Qian Shuai, Hongyan Ahooghalandari, Parvin Gylfe, Erik Tengholm, Anders |
author_sort | Yu, Qian |
collection | PubMed |
description | AIMS/HYPOTHESIS: Glucagon is critical for normal glucose homeostasis and aberrant secretion of the hormone aggravates dysregulated glucose control in diabetes. However, the mechanisms by which glucose controls glucagon secretion from pancreatic alpha cells remain elusive. The aim of this study was to investigate the role of the intracellular messenger cAMP in alpha-cell-intrinsic glucose regulation of glucagon release. METHODS: Subplasmalemmal cAMP and Ca(2+) concentrations were recorded in isolated and islet-located alpha cells using fluorescent reporters and total internal reflection microscopy. Glucagon secretion from mouse islets was measured using ELISA. RESULTS: Glucose induced Ca(2+)-independent alterations of the subplasmalemmal cAMP concentration in alpha cells that correlated with changes in glucagon release. Glucose-lowering-induced stimulation of glucagon secretion thus corresponded to an elevation in cAMP that was independent of paracrine signalling from insulin or somatostatin. Imposed cAMP elevations stimulated glucagon secretion and abolished inhibition by glucose elevation, while protein kinase A inhibition mimicked glucose suppression of glucagon release. CONCLUSIONS/INTERPRETATION: Glucose concentrations in the hypoglycaemic range control glucagon secretion by directly modulating the cAMP concentration in alpha cells independently of paracrine influences. These findings define a novel mechanism for glucose regulation of glucagon release that underlies recovery from hypoglycaemia and may be disturbed in diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-019-4857-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users. |
format | Online Article Text |
id | pubmed-6560012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-65600122019-06-26 Glucose controls glucagon secretion by directly modulating cAMP in alpha cells Yu, Qian Shuai, Hongyan Ahooghalandari, Parvin Gylfe, Erik Tengholm, Anders Diabetologia Article AIMS/HYPOTHESIS: Glucagon is critical for normal glucose homeostasis and aberrant secretion of the hormone aggravates dysregulated glucose control in diabetes. However, the mechanisms by which glucose controls glucagon secretion from pancreatic alpha cells remain elusive. The aim of this study was to investigate the role of the intracellular messenger cAMP in alpha-cell-intrinsic glucose regulation of glucagon release. METHODS: Subplasmalemmal cAMP and Ca(2+) concentrations were recorded in isolated and islet-located alpha cells using fluorescent reporters and total internal reflection microscopy. Glucagon secretion from mouse islets was measured using ELISA. RESULTS: Glucose induced Ca(2+)-independent alterations of the subplasmalemmal cAMP concentration in alpha cells that correlated with changes in glucagon release. Glucose-lowering-induced stimulation of glucagon secretion thus corresponded to an elevation in cAMP that was independent of paracrine signalling from insulin or somatostatin. Imposed cAMP elevations stimulated glucagon secretion and abolished inhibition by glucose elevation, while protein kinase A inhibition mimicked glucose suppression of glucagon release. CONCLUSIONS/INTERPRETATION: Glucose concentrations in the hypoglycaemic range control glucagon secretion by directly modulating the cAMP concentration in alpha cells independently of paracrine influences. These findings define a novel mechanism for glucose regulation of glucagon release that underlies recovery from hypoglycaemia and may be disturbed in diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-019-4857-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users. Springer Berlin Heidelberg 2019-04-05 2019 /pmc/articles/PMC6560012/ /pubmed/30953108 http://dx.doi.org/10.1007/s00125-019-4857-6 Text en © The Author(s) 2019 Open Access This 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. |
spellingShingle | Article Yu, Qian Shuai, Hongyan Ahooghalandari, Parvin Gylfe, Erik Tengholm, Anders Glucose controls glucagon secretion by directly modulating cAMP in alpha cells |
title | Glucose controls glucagon secretion by directly modulating cAMP in alpha cells |
title_full | Glucose controls glucagon secretion by directly modulating cAMP in alpha cells |
title_fullStr | Glucose controls glucagon secretion by directly modulating cAMP in alpha cells |
title_full_unstemmed | Glucose controls glucagon secretion by directly modulating cAMP in alpha cells |
title_short | Glucose controls glucagon secretion by directly modulating cAMP in alpha cells |
title_sort | glucose controls glucagon secretion by directly modulating camp in alpha cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560012/ https://www.ncbi.nlm.nih.gov/pubmed/30953108 http://dx.doi.org/10.1007/s00125-019-4857-6 |
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