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Updated: May 13, 2025

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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
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DEC1 Regulates Human β Cell Functional Maturation and Circadian Rhythm
Biorxiv : the Preprint Server for Biology
|April 16, 2025
Summary
A key protein, DEC1, is crucial for maturing stem cell-derived islet organoids for diabetes therapy. It ensures proper insulin release and glucose response, vital for functional cell replacement.
Area of Science:
- Endocrinology
- Stem Cell Biology
- Chronobiology
Background:
- Stem cell-derived islet (SC-islet) organoids show promise for diabetes cell replacement therapy.
- Immature function of SC-islets, particularly the lack of a mature beta-cell circadian clock, limits their therapeutic potential.
- The role of circadian rhythms in regulating beta-cell maturation is not well understood.
Purpose of the Study:
- To investigate the role of the circadian transcription factor DEC1 in the maturation of stem cell-derived beta-cells.
- To determine how DEC1 influences insulin responsiveness and glucose metabolism in SC-islets.
- To elucidate the mechanisms by which DEC1 synchronizes circadian rhythms and promotes SC-islet maturity.
Main Methods:
- Generation of SC-islet organoids from human pluripotent stem cells with and without DEC1 ablation.
- Assessment of insulin release capacity, glucose threshold, and metabolic function (glycolysis, oxidative metabolism) in SC-islets.
- Analysis of maturity-linked effector expression and circadian clock synchronization.
Main Results:
- DEC1-ablated SC-islets formed normally but exhibited impaired insulin release and elevated glucose thresholds, failing to mature *in vitro* or *in vivo*.
- The functional deficits in DEC1-ablated SC-islets were linked to reduced glucose utilization, blunted metabolism, and impaired insulin exocytosis.
- Restoring metabolic flux partially rescued the functional deficits in DEC1-ablated SC-islets.
- DEC1 was essential for synchronizing circadian insulin secretion rhythms and clock machinery, thereby promoting SC-islet maturity.
Conclusions:
- DEC1 is a critical regulator of human beta-cell maturation, linking circadian control to functional development.
- DEC1 enhances SC-islet maturity by optimizing glucose responsiveness, metabolic function, and circadian synchronization.
- Targeting DEC1 may be a viable strategy to improve the therapeutic efficacy of stem cell-derived islets for diabetes treatment.
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