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

Petrenko, Volodymyr; Saini, Camille; Morele Giovannoni, Laurianne; Gobet, Cedric; Sage, Daniel; Unser, Michael; Heddad Masson, Mounia; Gu, Guoqiang; Bosco, Domenico; Gachon, Frédéric; Philippe, Jacques; Dibner, Charna

doi:10.1101/gad.290379.116

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Title		Pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression
Authors		Petrenko, Volodymyr Saini, Camille Morele Giovannoni, Laurianne Gobet, Cedric Sage, Daniel Unser, Michael Heddad Masson, Mounia Gu, Guoqiang Bosco, Domenico Gachon, Frédéric Philippe, Jacques Dibner, Charna show all authors [1 - 12]
Published in		Genes and Development. 2017, vol. 31, no. 4, p. 383-398
Abstract		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.
Keywords		Animals — Cells — Cultured — Circadian Clocks/drug effects/physiology — Colforsin/pharmacology — Enzyme Activators/pharmacology — Gene Expression Profiling — Gene Expression Regulation/drug effects — Glucagon/blood/secretion — Glucagon-Secreting Cells/drug effects/physiology — Insulin/blood/secretion — Insulin-Secreting Cells/drug effects/physiology — Mice — Models — Animal — Sequence Analysis — RNA — Time Factors
Identifiers		DOI: 10.1101/gad.290379.116 PMID: 28275001
Full text		Article (Published version) (1.9 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département de chirurgie Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique
Research groups		Développement du tube digestif chez les vertébrés (900) Endocrinologie et horloge circadienne (948) La transplantation d'îlots de Langerhans (623)
Citation (ISO format)		PETRENKO, Volodymyr et al. Pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression. In: Genes and Development, 2017, vol. 31, n° 4, p. 383-398. doi: 10.1101/gad.290379.116 https://archive-ouverte.unige.ch/unige:100675