RT Journal Article
T1 Pancreatic β cells overexpressing hIAPP impaired mitophagy and unbalanced mitochondrial dynamics
A1 García Hernández Miriam, 
A1 García Aguilar, Ana
A1 Burillo Maldonado, Jesús
A1 Gómez Oca, Raquel
A1 Manca, María Antonietta
A1 Novials, Ana
A1 Alcarraz-Vizarrán, Gema
A1 Guillén Viejo, Carlos
A1 Benito De Las Heras, Manuel R.
AB Human islet amyloid polypeptide (hIAPP), or amylin, has the tendency to aggregate into insoluble amyloid fibrils, a typical feature of islets from type 2 diabetes individuals. Thus, we investigated comparatively the impact of hIAPP on key pathways involved in pancreatic beta survival. INS1E-hIAPP cells present a hyperactivation of MTORC1 and an inhibition of autophagy signaling, those cells showing an increase in cell size. Resveratrol, a MTORC1 inhibitor, can reverse TSC2 degradation that occurs in INS1E-hIAPP cells and diminished MTORC1 hyperactivation with concomitant autophagy stimulation. At the same time, a blockade in mitophagy was found in INS1E-hIAPP cells, as compared with control or INS1E-rIAPP cells. Consistently, human amylin overexpression generates a basal induction of nitrotyrosine levels and polyubiquitinated aggregates. Failure of the protein degradation machinery finally results in an accumulation of damaged and fissioned mitochondria, ROS production, and increased susceptibility to endoplasmic reticulum (ER)-stress-induced apoptosis. Overall, hIAPP overexpression in INS1E cells induced MTORC1 activation and mitophagy inhibition, favoring a pro-fission scenario of damaged mitochondria, these cells turn out to be more susceptible to the ER-stress-induced apoptosis and malfunction.
PB Nature Publishing Group UK
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/115680
UL https://hdl.handle.net/20.500.14352/115680
LA eng
NO Hernández MG, García-Aguilar A, Burillo J, Oca RG, Manca MA, Novials A, Alcarraz-Vizan G, Guillén C, Benito M. Pancreatic β cells overexpressing hIAPP impaired mitophagy and unbalanced mitochondrial dynamics. Cell Death Dis. 2018 May 1;9(5):481. doi: 10.1038/s41419-018-0533-x. PMID: 29705815; PMCID: PMC5924657.
NO Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 7 abr 2025