2026-06-01T07:36:27Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1154872025-03-18T15:18:41Zcom_20.500.14352_14col_20.500.14352_15

Pancreatic b-Cell failure mediated by mTORC1 hyperactivity and autophagic impairment Bartolomé, Alberto Kimura-Koyanagi, Maki Asahara, Shun-Ichiro Guillén Viejo, Carlos Inoue, Hiroyuki Teruyama, Kyoko Shimizu, Shinobu Kanno, Ayumi García Aguilar, Ana Koike, Masato Uchiyama, Yasuo Benito, Manuel Noda, Tetsuo Kido, Yoshiaki 577.1 577.2 Biología celular (Farmacia) Biología molecular (Farmacia) Bioquímica (Farmacia) 2403 Bioquímica 2407 Biología Celular 2415 Biología Molecular Hyperactivation 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 failure Ministry of Education, Culture, Sports, Science and Technology–Japan Ministerio de Ciencia e Innovación (España) Depto. de Bioquímica y Biología Molecular Fac. de Farmacia TRUE pub 2025-01-22T08:35:01Z 2025-01-22T08:35:01Z 2014 journal article VoR https://hdl.handle.net/20.500.14352/115487 XXXX-XXXX 10.2337/db13-0970 eng info:eu-repo/grantAgreement/MICINN//SAF2011-22555/ES/PAPEL DE LA FORMACION Y FUNCION DEL TEJIDO ADIPOSO MARRON SOBRE LA PATOGENESIS DE LA OBESIDAD: RECUPERACION DE LA FUNCION TERMOGENICA MARRON COMO TERAPIA ANTIOBESIDAD/ Bartolomé, 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. Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ metadata only access application/pdf American Diabetes Association