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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
Autonomous and self-sustained circadian oscillators displayed in human islet cells
1Division of Endocrinology, Diabetes and Nutrition, University Hospital of Geneva, Aile Jura 4-771.2, Rue Gabrielle-Perret-Gentil 4, CH-1211 Geneva, Switzerland.
Diabetologia
|December 18, 2012
Summary
Human pancreatic islets exhibit robust, cell-autonomous circadian gene expression rhythms. These internal biological clocks are synchronized between beta and non-beta cells, offering new insights into islet function and diabetes.
Area of Science:
- Endocrinology
- Chronobiology
- Molecular Biology
Background:
- Circadian clocks regulate islet function and are implicated in type 2 diabetes development.
- Previous studies focused on rodent models, leaving human islet circadian biology largely unexplored.
Purpose of the Study:
- To investigate circadian gene expression in human pancreatic islets and isolated beta cells.
- To characterize the oscillatory properties of these cellular clocks.
Main Methods:
- Utilized bioluminescence recording in cultured human islets with a Bmal1-luciferase reporter.
- Employed fluorescence labeling for beta cells and time-lapse microscopy for oscillation analysis.
- Assessed transcript levels of core clock genes and key islet transcription factors.
Main Results:
- Demonstrated self-sustained circadian oscillations of Bmal1 expression in human islets and dispersed islet cells.
- Identified circadian expression patterns for BMAL1, CRY1, REV-ERBα, PER1-3, and DBP transcripts.
- Observed synchronized circadian oscillations between human beta and non-beta cells.
Conclusions:
- Provided the first compelling evidence for high-amplitude, cell-autonomous circadian oscillators in human pancreatic islets.
- Confirmed synchronization of circadian clocks between different cell types within human islets.
- These findings highlight the importance of the islet circadian clock in human physiology.
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