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

作者: Daniel Sage , Michael Unser , Mounia Heddad Masson , Guoqiang Gu , Domenico Bosco

DOI: 10.1101/GAD.290379.116

关键词: BiologyIsletMolecular biologyGlucagon secretionCircadian clockReporter geneGene expression profilingTranscriptomeCell biologyRegulation of gene expressionGene expression

摘要: 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 did not explore the interplay between α-cell β-cell clocks. We performed a parallel analysis molecular properties using mouse model expressing three reporter genes: one labeling α cells, specific for β third monitoring expression. Thus, phase entrainment properties, expression, functional outputs clockworks could be assessed vivo vitro at population single-cell level. These experiments showed that α-cellular β-cellular clocks are oscillating with distinct phases vitro. Diurnal transcriptome separated cells revealed high number genes key roles physiology, including regulators glucose sensing hormone secretion, differentially expressed cell types. Moreover, temporal glucagon exhibited oscillatory profiles both Altogether, our data indicate differential characteristics an important feature coordination endocrine function

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