Metabolic reprogramming drives pancreatic β cell neogenesis from α cells
Yufeng Zhang1,2, Guangxing Lu1, Wenhao Xie1
1State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Pharmaceutical Sciences, Zhongshan Hospital and School of Life Sciences, Fudan University, Shanghai, China.
Nature Chemical Biology
|August 7, 2026
Summary
Researchers identified PRC2 inhibitors that reprogram alpha cells into beta cells. Metabolic reprogramming using 6-phosphogluconate stimulates beta cell regeneration and improves diabetes.
Area of Science:
- Endocrinology and Metabolism
- Cell Biology
- Regenerative Medicine
Background:
- Loss of functional beta cells is a primary characteristic of diabetes.
- Restoring beta cell mass is a key therapeutic objective for diabetes.
- Converting islet alpha cells to insulin-producing beta cells is a potential strategy.
Purpose of the Study:
- To identify novel therapeutic strategies for diabetes by exploring beta cell regeneration.
- To investigate the role of PRC2 inhibitors in inducing beta cell-like features in alpha cells.
- To explore metabolic reprogramming as a method to stimulate beta cell regeneration.
Main Methods:
- Utilized PRC2 inhibitors to modulate the AR-ETV1 complex in alpha cells.
- Investigated the effects of AR inhibition on glycogen synthesis and the pentose phosphate pathway.
- Employed direct metabolic reprogramming with methyl esterified 6-phosphogluconate.
Main Results:
- PRC2 inhibitors were found to be potent inducers of beta cell-enriched gene expression in alpha cells.
- AR inhibition suppressed glycogen synthesis and enhanced the pentose phosphate pathway.
- Metabolic reprogramming with 6-phosphogluconate induced beta cell-like features, stimulated regeneration, and ameliorated diabetes.
Conclusions:
- Metabolic reprogramming is a key driver of beta cell regeneration.
- PRC2 inhibitors and targeted metabolic interventions show promise for diabetes therapy.
- This study highlights a novel therapeutic avenue for treating diabetes by regenerating beta cells.
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