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Genes Dev. 2017 Feb 15;31(4):383-398. doi: 10.1101/gad.290379.116. Epub 2017 Mar 8.

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

Author information

1
Endocrinology, Diabetes, Hypertension, and Nutrition, University Hospital of Geneva, CH-1211 Geneva, Switzerland.
2
Department of Cellular Physiology and Metabolism, Diabetes Center, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland.
3
Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, CH-1211 Geneva, Switzerland.
4
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
5
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
6
Biomedical Imaging Group, EPFL, CH-1015 Lausanne, Switzerland.
7
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37240, USA.
8
Department of Surgery, Cell Isolation and Transplantation Centre, University Hospital of Geneva, CH-1211 Geneva, Switzerland.

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:

RNA sequencing; circadian clock; insulin/glucagon secretion; mouse α cells and β cells; single-cell bioluminescence–fluorescence time-lapse microscopy

PMID:
28275001
PMCID:
PMC5358758
DOI:
10.1101/gad.290379.116
[Indexed for MEDLINE]
Free PMC Article

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