par Suleiman, Mara;Sawatani, Toshiaki 
;Tesi, Marta;Yi, Xiaoyan ;Papadopoulou, Theodora ;Rufer, Chantal ;Lytrivi, Maria ;Bosi, Emanuele;Burdet, Frederic;Fantuzzi, Federica ;De Luca, Carmela;Sebastiani, Guido;Saponaro, Chiara;Pugliese, Licia Anna;Del Guerra, Silvia;Pocai, Alessandro;De Simone, Paolo ;Ghinolfi, Davide;Boggi, Ugo;Kessler, Camille;Grieco, Giuseppina Emanuela;Fignani, Daniela;Kerr-Conte, Julie;Pattou, François;Nacher, Montserrat;Montanya, Eduard;Mourad, Nizar N.I.;Buemi, Antoine;Citi, Valentina;Martelli, Alma;Benedetti, Giada;Calderone, Vincenzo;Rossi, Leonardo;Paolicchi, Aldo;Cardarelli, Francesco;Dotta, Francesco;Eizirik, Decio L. ;Ibberson, Mark;Marchetti, Piero;Cnop, Miriam ;Marselli, Lorella
Référence Science advances, 11, 41, page (eads2905)
Publication Publié, 2025-10-01
;Tesi, Marta;Yi, Xiaoyan ;Papadopoulou, Theodora ;Rufer, Chantal ;Lytrivi, Maria ;Bosi, Emanuele;Burdet, Frederic;Fantuzzi, Federica ;De Luca, Carmela;Sebastiani, Guido;Saponaro, Chiara;Pugliese, Licia Anna;Del Guerra, Silvia;Pocai, Alessandro;De Simone, Paolo ;Ghinolfi, Davide;Boggi, Ugo;Kessler, Camille;Grieco, Giuseppina Emanuela;Fignani, Daniela;Kerr-Conte, Julie;Pattou, François;Nacher, Montserrat;Montanya, Eduard;Mourad, Nizar N.I.;Buemi, Antoine;Citi, Valentina;Martelli, Alma;Benedetti, Giada;Calderone, Vincenzo;Rossi, Leonardo;Paolicchi, Aldo;Cardarelli, Francesco;Dotta, Francesco;Eizirik, Decio L. ;Ibberson, Mark;Marchetti, Piero;Cnop, Miriam ;Marselli, LorellaRéférence Science advances, 11, 41, page (eads2905)
Publication Publié, 2025-10-01
Article révisé par les pairs
| Résumé : | 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. |
