Authors
Yufeng Zhang, Guangxing Lu, Wenhao Xie, Peng Xu, Cenxi Liu, Olga Babosova, Jamie Christopher Reilly, Zhehui Li, Leshi Chen, Liying Zhou, Jing Gao, Lennart Enders, Xuelian Xiong, Mingyu Li, Stefan Kubicek, Bing Zhao, Zhe Feng, Biao Yu, Lu Zhou, He Huang, Jin Li
Published in
Nature chemical biology. Aug 07, 2026. Epub Aug 07, 2026.
Abstract
Loss of functional β cells is a hallmark of diabetes, and restoring β cell mass remains a critical goal in the quest for a specific therapy. One potential strategy is to convert non-β cells in the islet, such as α cells, into insulin-producing cells. Although several compounds have been identified to induce β cell-like features in α cells, none have been successfully translated into clinical applications. In this study, we identify PRC2 inhibitors as potent inducers of β cell-enriched gene expression in α cells, acting through modulation of the AR-ETV1 complex. AR inhibition suppresses glycogen synthesis and enhances the pentose phosphate pathway. Direct metabolic reprogramming with methyl esterified 6-phosphogluconate, an intermediate metabolite of the pentose phosphate pathway, induces β cell-like features in α cells, stimulates β cell regeneration and ameliorates diabetes. Our findings demonstrate that metabolic reprogramming drives β cell regeneration and highlight a promising therapeutic strategy for diabetes.
PMID:
42567976
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.
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