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Updated: Jan 16, 2026
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A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform
Published on: July 16, 2016
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I-BET151 modulates glucokinase gene expression and beta cell function in part through changes in FOXO1 expression.
Qing Wei Calvin Ho1, James A Miller1, Divya Gunaseelan1
1Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Republic of Singapore.
Diabetologia
|September 26, 2025
Summary
BET inhibition may harm pancreatic beta cell function. This study found that I-BET151 reduced glucose regulation and insulin secretion in mice, impacting key beta cell genes. Caution is advised for BET inhibitor therapies.
Area of Science:
- Epigenetics and molecular biology
- Endocrinology and metabolism
- Cancer biology
Background:
- Bromodomain and extra-terminal (BET) proteins are epigenetic readers modulating gene transcription.
- BET proteins are implicated in diseases like cancer and type 1 diabetes.
- Potential off-target effects of BET inhibitors on host cells require investigation.
Purpose of the Study:
- To investigate the secondary effects of BET inhibition on pancreatic beta cell function.
- To determine the impact of the BET inhibitor I-BET151 on glucose homeostasis and insulin secretion.
- To identify molecular mechanisms underlying BET inhibition's effects on beta cells.
Main Methods:
- In vitro, ex vivo, and in vivo studies using the BET inhibitor I-BET151.
- Glucose tolerance tests (GTTs) and insulin tolerance tests (ITTs) in mice.
- Glucose-stimulated insulin secretion assays and transcriptomic analysis in rodent and human islets.
Main Results:
- I-BET151 administration increased glucose excursions and reduced insulin responses in healthy and diabetic mice.
- I-BET151 significantly decreased the expression of essential beta cell function genes (e.g., Hnf4α, Gck, Hnf1α, Glut2).
- Transcriptomic analysis revealed downregulation of the PI3K-Akt pathway, with FOXO1 modulation partially rescuing effects.
Conclusions:
- BET inhibition may have detrimental effects on pancreatic beta cell function.
- High concentrations of BET inhibitors could negatively impact glucose regulation and insulin secretion.
- Therapeutic use of BET inhibitors requires caution due to potential adverse effects on beta cells.
Keywords:
BET protein inhibitorsBeta cellsEpigenetic modulatorsFOXO1GCKHNF4aI-BET151INS-1EMODYPancreatic isletsMore Related Videos
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