2026-06-27T16:20:43Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/68172024-07-30T14:00:24Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Burillo Maldonado, Jesús author Fernández Rhodes, M. author Piquero, M. author López-Alvarado Gutiérrez, María Pilar author Menéndez Ramos, José Carlos author Jiménez, B. author González Blanco, C. author Marqués, P. author Guillén Viejo, Carlos author Benito De Las Heras, Manuel R. 2023-06-17T08:22:19Z 2023-06-17T08:22:19Z 2021-01-27 Burillo Maldonado, J., Fernández Rhodes, M., Piquero, M. et al. «Human Amylin Aggregates Release within Exosomes as a Protective Mechanism in Pancreatic β Cells: Pancreatic β-Hippocampal Cell Communication». Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, vol. 1868, n.o 5, abril de 2021, p. 118971. DOI.org (Crossref), https://doi.org/10.1016/j.bbamcr.2021.118971. 0167-4889 10.1016/j.bbamcr.2021.118971 https://hdl.handle.net/20.500.14352/6817 https://doi.org/10.1016/j.bbamcr.2021.118971 Pancreatic β cells are essential in the maintenance of glucose homeostasis during the progression to type 2 Diabetes Mellitus (T2DM), generating compensatory hyperinsulinemia to counteract insulin resistance. It is well known, that throughout the process there is an increased mTORC1 signaling pathway, with an impairment in different quality control systems including ubiquitin-proteasome system and autophagy. In addition, under this situation, pancreatic β cells start to accumulate amylin protein (IAPP) in aggregates, and this accumulation contributes to the failure of autophagy, damaging different organelles such as plasma membrane, endoplasmic reticulum, mitochondria, and others. Here, we report that IAPP can be incorporated to multivesicular bodies (MVB) and secreted into exosomes, a mechanism responsible for the exportation of these toxic aggregates as vehicles of cell to cell communication. On this regard, we have demonstrated that the exosomes bearing toxic hIAPP released from pancreatic β cells are capable to induce hyperactivation of mTORC1 signaling, a failure in the autophagic cellular quality control, and favor pro-fission status of the mitochondrial dynamics in hippo-campal cells. In summary, our results show that harmful accumulation of hIAPP in pancreatic β cells may be detoxified by the release of exosomes, which may be captured by endocytosis mechanism damaging neuronal hippocampal cells, which suggest an underlying molecular mechanism to the link between type 2 diabetes and neurodegenerative diseases. eng Atribución-NoComercial-SinDerivadas 3.0 España Human amylin aggregates release within exosomes as a protective mechanism in pancreatic β cells: Pancreatic β-hippocampal cell communication journal article URL https://docta.ucm.es/bitstreams/78c55d1a-872e-4690-91ea-e6cfbc0738d5/download File MD5 d3f7ef18683acd3d12715ebee9cb06d4 5918009 application/pdf 1-s2.0-S0167488921000252-main.pdf URL https://docta.ucm.es/bitstreams/b071d81c-38f9-4d96-8f17-0c5e88d5642e/download File MD5 fc5dea369278c5bd830da5c11129a842 62617 text/plain 1-s2.0-S0167488921000252-main.pdf.txt