Bartolomé, AlbertoKimura-Koyanagi, MakiAsahara, Shun-IchiroGuillén Viejo, CarlosInoue, HiroyukiTeruyama, KyokoShimizu, ShinobuKanno, AyumiGarcía Aguilar, AnaKoike, MasatoUchiyama, YasuoBenito, ManuelNoda, TetsuoKido, Yoshiaki2025-01-222025-01-222014Bartolomé, A., Kimura-Koyanagi, M., Asahara, S. I., Guillén, C., Inoue, H., Teruyama, K., ... & Kido, Y. (2014). Pancreatic β-cell failure mediated by mTORC1 hyperactivity and autophagic impairment. Diabetes, 63(9), 2996-3008.10.2337/db13-0970https://hdl.handle.net/20.500.14352/115487Hyperactivation of the mammalian target of rapamycin complex 1 (mTORC1) in β-cells is usually found as a consequence of increased metabolic load. Although it plays an essential role in β-cell compensatory mechanisms, mTORC1 negatively regulates autophagy. Using a mouse model with β-cell–specific deletion of Tsc2 (βTsc2−/−) and, consequently, mTORC1 hyperactivation, we focused on the role that chronic mTORC1 hyperactivation might have on β-cell failure. mTORC1 hyperactivation drove an early increase in β-cell mass that later declined, triggering hyperglycemia. Apoptosis and endoplasmic reticulum stress markers were found in islets of older βTsc2−/− mice as well as accumulation of p62/SQSTM1 and an impaired autophagic response. Mitochondrial mass was increased in β-cells of βTsc2−/− mice, but mitophagy was also impaired under these circumstances. We provide evidence of β-cell autophagy impairment as a link between mTORC1 hyperactivation and mitochondrial dysfunction that probably contributes to β-cell failureengAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://doi.org/10.2337/db13-0970metadata only access577.1577.2Biología celular (Farmacia)Biología molecular (Farmacia)Bioquímica (Farmacia)2403 Bioquímica2407 Biología Celular2415 Biología Molecular