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Pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression

A critical role of circadian oscillators in orchestrating insulin secretion and islet gene transcription has been demonstrated recently. However, these studies focused on whole islets and did not explore the interplay between α-cell and β-cell clocks. We performed a parallel analysis of the molecula...

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Autores principales: Petrenko, Volodymyr, Saini, Camille, Giovannoni, Laurianne, Gobet, Cedric, Sage, Daniel, Unser, Michael, Heddad Masson, Mounia, Gu, Guoqiang, Bosco, Domenico, Gachon, Frédéric, Philippe, Jacques, Dibner, Charna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358758/
https://www.ncbi.nlm.nih.gov/pubmed/28275001
http://dx.doi.org/10.1101/gad.290379.116
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author Petrenko, Volodymyr
Saini, Camille
Giovannoni, Laurianne
Gobet, Cedric
Sage, Daniel
Unser, Michael
Heddad Masson, Mounia
Gu, Guoqiang
Bosco, Domenico
Gachon, Frédéric
Philippe, Jacques
Dibner, Charna
author_facet Petrenko, Volodymyr
Saini, Camille
Giovannoni, Laurianne
Gobet, Cedric
Sage, Daniel
Unser, Michael
Heddad Masson, Mounia
Gu, Guoqiang
Bosco, Domenico
Gachon, Frédéric
Philippe, Jacques
Dibner, Charna
author_sort Petrenko, Volodymyr
collection PubMed
description A critical role of circadian oscillators in orchestrating insulin secretion and islet gene transcription has been demonstrated recently. However, these studies focused on whole islets and did not explore the interplay between α-cell and β-cell clocks. We performed a parallel analysis of the molecular properties of α-cell and β-cell oscillators using a mouse model expressing three reporter genes: one labeling α cells, one specific for β cells, and a third monitoring circadian gene expression. Thus, phase entrainment properties, gene expression, and functional outputs of the α-cell and β-cell clockworks could be assessed in vivo and in vitro at the population and single-cell level. These experiments showed that α-cellular and β-cellular clocks are oscillating with distinct phases in vivo and in vitro. Diurnal transcriptome analysis in separated α and β cells revealed that a high number of genes with key roles in islet physiology, including regulators of glucose sensing and hormone secretion, are differentially expressed in these cell types. Moreover, temporal insulin and glucagon secretion exhibited distinct oscillatory profiles both in vivo and in vitro. Altogether, our data indicate that differential entrainment characteristics of circadian α-cell and β-cell clocks are an important feature in the temporal coordination of endocrine function and gene expression.
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spelling pubmed-53587582017-08-15 Pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression Petrenko, Volodymyr Saini, Camille Giovannoni, Laurianne Gobet, Cedric Sage, Daniel Unser, Michael Heddad Masson, Mounia Gu, Guoqiang Bosco, Domenico Gachon, Frédéric Philippe, Jacques Dibner, Charna Genes Dev Research Paper A critical role of circadian oscillators in orchestrating insulin secretion and islet gene transcription has been demonstrated recently. However, these studies focused on whole islets and did not explore the interplay between α-cell and β-cell clocks. We performed a parallel analysis of the molecular properties of α-cell and β-cell oscillators using a mouse model expressing three reporter genes: one labeling α cells, one specific for β cells, and a third monitoring circadian gene expression. Thus, phase entrainment properties, gene expression, and functional outputs of the α-cell and β-cell clockworks could be assessed in vivo and in vitro at the population and single-cell level. These experiments showed that α-cellular and β-cellular clocks are oscillating with distinct phases in vivo and in vitro. Diurnal transcriptome analysis in separated α and β cells revealed that a high number of genes with key roles in islet physiology, including regulators of glucose sensing and hormone secretion, are differentially expressed in these cell types. Moreover, temporal insulin and glucagon secretion exhibited distinct oscillatory profiles both in vivo and in vitro. Altogether, our data indicate that differential entrainment characteristics of circadian α-cell and β-cell clocks are an important feature in the temporal coordination of endocrine function and gene expression. Cold Spring Harbor Laboratory Press 2017-02-15 /pmc/articles/PMC5358758/ /pubmed/28275001 http://dx.doi.org/10.1101/gad.290379.116 Text en © 2017 Petrenko et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Petrenko, Volodymyr
Saini, Camille
Giovannoni, Laurianne
Gobet, Cedric
Sage, Daniel
Unser, Michael
Heddad Masson, Mounia
Gu, Guoqiang
Bosco, Domenico
Gachon, Frédéric
Philippe, Jacques
Dibner, Charna
Pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression
title Pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression
title_full Pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression
title_fullStr Pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression
title_full_unstemmed Pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression
title_short Pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression
title_sort pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358758/
https://www.ncbi.nlm.nih.gov/pubmed/28275001
http://dx.doi.org/10.1101/gad.290379.116
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