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Updated: May 25, 2026
06:53
Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
Regulation of core clock genes in human islets
Jelena A Stamenkovic1, Anders H Olsson, Cecilia L Nagorny
1Department of Clinical Sciences in Malmö, Units of Molecular Metabolism, Lund University Diabetes Centre, Scania University Hospital, SE-205 02, Malmö, Sweden. Jelena.Stamenkovic@med.lu.se
Metabolism: Clinical and Experimental
|February 7, 2012
Summary
Circadian clock genes, like PER2, PER3, and CRY2, are less abundant in human islets from individuals with type 2 diabetes. Lower clock gene expression correlates with impaired insulin secretion and poorer glycemic control, suggesting a role in diabetes pathophysiology.
Area of Science:
- Endocrinology
- Molecular Biology
- Chronobiology
Background:
- Mammalian cells express clock genes regulating circadian rhythms via transcriptional-translational feedback loops.
- Genome-wide association studies suggest a link between CRY2 gene variants and elevated fasting glucose.
- The role of clock genes in the pathogenesis of type 2 diabetes mellitus (T2DM) remains to be fully elucidated.
Purpose of the Study:
- To investigate the expression of core clock genes in human islets from donors with and without T2DM.
- To determine the functional relevance of clock gene expression in relation to insulin secretion and glycemic control.
Main Methods:
- Microarray and quantitative real-time polymerase chain reaction (qPCR) were used to assess mRNA levels of CLOCK, BMAL-1, PER1-3, and CRY1-2 in human islets.
- Insulin secretion and content were measured using radioimmunoassay.
- In vitro models exposed human islets to high glucose and palmitate conditions.
Main Results:
- mRNA levels of PER2, PER3, and CRY2 were significantly reduced in islets from T2DM donors.
- PER2, PER3, and CRY2 mRNA levels positively correlated with insulin content.
- PER3 and CRY2 mRNA levels negatively correlated with glycated hemoglobin levels.
- PER3 mRNA expression decreased in human islets exposed to high glucose and palmitate in vitro.
Conclusions:
- Core clock gene expression is altered in human islets affected by type 2 diabetes.
- Reduced expression of circadian clock genes, specifically PER2, PER3, and CRY2, may contribute to islet dysfunction in T2DM.
- Circadian clock gene perturbations are implicated in the pathophysiology of type 2 diabetes mellitus.
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