RT Journal Article
T1 Pancreatic b-Cell failure mediated by mTORC1 hyperactivity and autophagic impairment
A1 Bartolomé, Alberto
A1 Kimura-Koyanagi, Maki
A1 Asahara, Shun-Ichiro
A1 Guillén Viejo, Carlos
A1 Inoue, Hiroyuki
A1 Teruyama, Kyoko
A1 Shimizu, Shinobu
A1 Kanno, Ayumi
A1 García Aguilar, Ana
A1 Koike, Masato
A1 Uchiyama, Yasuo
A1 Benito, Manuel
A1 Noda, Tetsuo
A1 Kido, Yoshiaki
AB 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
PB American Diabetes Association
YR 2014
FD 2014
LK https://hdl.handle.net/20.500.14352/115487
UL https://hdl.handle.net/20.500.14352/115487
LA eng
NO 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.
NO Ministry of Education, Culture, Sports, Science and Technology–Japan
NO Ministerio de Ciencia e Innovación (España)
DS Docta Complutense
RD 7 abr 2025