Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early ß-cell damage in obesity and diabetes
Por:
Altamirano-Bustamante N.F., Garrido-Magaña E., Morán E., Calderón A., Pasten-Hidalgo K., Castillo-Rodríguez R.A., Rojas G., Lara-Martínez R., Leyva-García E., Larralde-Laborde M., Domíguez G., Murata C., Margarita-Vazquez Y., Payro R., Barbosa M., Valderrama A., Montesinos H., Domínguez-Camacho A., García-Olmos V.H., Ferrer R., Medina-Bravo P.G., Santoscoy F., Revilla-Monsalve C., Jiménez-García L.F., Morán J., Villalobos-Alva J., Villalobos M.J., Calzada-León R., Altamirano P., Altamirano-Bustamante M.M.
Publicada:
1 ene 2020
Categoría:
Multidisciplinary
Resumen:
Background and aims This is the first time that obesity and diabetes mellitus (DM) as protein conformational diseases (PCD) are reported in children and they are typically diagnosed too late, when ß-cell damage is evident. Here we wanted to investigate the level of naturally-ocurring or real (not synthetic) oligomeric aggregates of the human islet amyloid polypeptide (hIAPP) that we called RIAO in sera of pediatric patients with obesity and diabetes. We aimed to reduce the gap between basic biomedical research, clinical practice-health decision making and to explore whether RIAO work as a potential biomarker of early ß-cell damage. Materials and methods We performed a multicentric collaborative, cross-sectional, analytical, ambispective and blinded study; the RIAO from pretreated samples (PTS) of sera of 146 pediatric patients with obesity or DM and 16 healthy children, were isolated, measured by sound indirect ELISA with novel anti-hIAPP cytotoxic oligomers polyclonal antibody (MEX1). We carried out morphological and functional studied and cluster-clinical data driven analysis. Results We demonstrated by western blot, Transmission Electron Microscopy and cell viability experiments that RIAO circulate in the blood and can be measured by ELISA; are elevated in serum of childhood obesity and diabetes; are neurotoxics and works as biomarkers of early ß-cell failure. We explored the range of evidence-based medicine clusters that included the RIAO level, which allowed us to classify and stratify the obesity patients with high cardiometabolic risk. Conclusions RIAO level increases as the number of complications rises; RIAOs > 3.35 µg/ml is a predictor of changes in the current indicators of ß-cell damage. We proposed a novel physio-pathological pathway and shows that PCD affect not only elderly patients but also children. Here we reduced the gap between basic biomedical research, clinical practice and health decision making. © 2020 Altamirano-Bustamante et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Filiaciones:
Instituto Nacional de Pediatría, México City, Mexico
UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico
Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
Cátedras CONACyT, Consejo Nacional de Ciencia y Tecnología, Mexico City, Mexico
Facultad de Ciencias, UNAM, Mexico City, Mexico
Instituto de Fisiología Celular, UNAM, Mexico City, Mexico
Hospital Infantil Federico Gómez, Mexico City, Mexico
All Open Access; Gold
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