{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:04:46Z","timestamp":1790042686024,"version":"4.0.1"},"reference-count":52,"publisher":"American Diabetes Association","issue":"9","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,9,1]]},"abstract":"<jats:p>Hyperactivation of the mammalian target of rapamycin complex 1 (mTORC1) in \u03b2-cells is usually found as a consequence of increased metabolic load. Although it plays an essential role in \u03b2-cell compensatory mechanisms, mTORC1 negatively regulates autophagy. Using a mouse model with \u03b2-cell\u2013specific deletion of Tsc2 (\u03b2Tsc2\u2212\/\u2212) and, consequently, mTORC1 hyperactivation, we focused on the role that chronic mTORC1 hyperactivation might have on \u03b2-cell failure. mTORC1 hyperactivation drove an early increase in \u03b2-cell mass that later declined, triggering hyperglycemia. Apoptosis and endoplasmic reticulum stress markers were found in islets of older \u03b2Tsc2\u2212\/\u2212 mice as well as accumulation of p62\/SQSTM1 and an impaired autophagic response. Mitochondrial mass was increased in \u03b2-cells of \u03b2Tsc2\u2212\/\u2212 mice, but mitophagy was also impaired under these circumstances. We provide evidence of \u03b2-cell autophagy impairment as a link between mTORC1 hyperactivation and mitochondrial dysfunction that probably contributes to \u03b2-cell failure.<\/jats:p>","DOI":"10.2337\/db13-0970","type":"journal-article","created":{"date-parts":[[2014,4,17]],"date-time":"2014-04-17T05:24:25Z","timestamp":1397712265000},"page":"2996-3008","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":123,"title":["Pancreatic \u03b2-Cell Failure Mediated by mTORC1 Hyperactivity and Autophagic Impairment"],"prefix":"10.2337","volume":"63","author":[{"given":"Alberto","family":"Bartolom\u00e9","sequence":"first","affiliation":[{"name":"Division of Medical Chemistry, Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan"},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain"},{"name":"CIBERDEM, Instituto de Salud 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