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2025-10-10

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cc-by-nc (c) Suleiman, M. et al., 2025
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/224529

Functional recovery of islet β cells in human type 2 diabetes: Transcriptome signatures unveil therapeutic approaches

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https://doi.org/10.1126/sciadv.ads2905

Resum

Remission of type 2 diabetes (T2D) can occur after hypocaloric diet, bariatric surgery, or pharmacological treatments and associates with improved β cell function. Here, we studied islets from nondiabetic (n = 15) and T2D (n = 21) donors. We examined whether T2D β cell dysfunction can be rescued, charted the underlying molecular mechanisms by RNA sequencing, and mined transcriptomes for drug targets. Glucose responsiveness of T2D β cells improved in 60% of preparations after 3-day culture in euglycemic conditions. This was accompanied by changes in expression of >400 genes involved in functional or inflammatory pathways. Drug repurposing and target identification analyses predicted chemical and genetic hits, including JAK inhibitors, which were validated in a β cell line, human islets, and db/db mice. Therefore, defective β cell glucose responsiveness in T2D can recover, demonstrating β cell functional plasticity. The recovery associates with transcriptomic traits, pointing to targetable defects to induce T2D remission.

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Diabetis no-insulinodependent, Expressió gènica, Glucosa, Animals

Matèries (anglès)

Non-insulin-dependent diabetes, Gene expression, Glucose, Animals

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Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

KERR-CONTE, Julie, PATTOU, François, NACHER, Montserrat, MONTANYA MIAS, Eduard, MOURAD, Nizar, BUEMI, Antoine, CITI, Valentina, MARTELLI, Alma, BENEDETTI, Giada, CALDERONE, Vicenzo, DE LUCA, Carmela, ROSSI, Leonardo, SEBASTIANI, Guido, PAOLICCHI, Aldo, SAPONARO, Chiara, CARDARELLI, Francesco, PUGLIESE, Licia anna, DOTTA, Francesco, DEL GUERRA, Silvia, EIZIRIK, Décio l., POCAI, Alessandro, IBBERSON, Mark, SIMONE, Paolo de, MARCHETTI, Piero, GHINOLFI, Davide, CNOP, Miriam, BOGGI, Ugo, KESSLER, Camille, SULEIMAN, Mara, SAWATANI, Toshiaki, TESI, Marta, YI, Xiaoyan, PAPADOPOULOU, Theodora, RUFER, Chantal, LYTRIVI, Maria, BOSI, Emanuele, BURDET, Frederic, FANTUZZI, Federica, MARSELLI, Lorella, GRIECO, Giuseppina emanuela, FIGNANI, Daniela. Functional recovery of islet β cells in human type 2 diabetes: Transcriptome signatures unveil therapeutic approaches. _Science Advances_. 2025. Vol. 11, núm. 41. [consulta: 23 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/224529]

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