GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE302nnn/GSE302889/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302889GEOGSEfalseMetabolic reprogramming drives pancreatic β cell neogenesis from α cells [RNA-Seq 2]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 yet 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 (PPP). Direct metabolic reprogramming with methyl esterified 6-phosphogluconate (ME-6-PG), an intermediate metabolite of the PPP, induces β cell-like features in α cells, stimulate β cell regeneration and ameliorates diabetes. Our findings demonstrate that metabolic reprogramming can drive β cell regeneration and highlight a promising therapeutic strategy for diabetes.2026/06/18GSE302889GSM9112969GSM9112968GSM9112967GSM9112973GSM9112972GSM9112971GSM9112970GSM9112976GSM9112975GSM911297424247302889Mus musculus