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PLoS One ; 15(8): e0237667, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32833960

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.


Asunto(s)
Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 2/patología , Células Secretoras de Insulina/patología , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Obesidad/patología , Estructura Cuaternaria de Proteína , Adolescente , Animales , Línea Celular , Supervivencia Celular , Células Cultivadas , Niño , Preescolar , Estudios Transversales , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Polipéptido Amiloide de los Islotes Pancreáticos/sangre , Polipéptido Amiloide de los Islotes Pancreáticos/toxicidad , Polipéptido Amiloide de los Islotes Pancreáticos/ultraestructura , Microscopía Electrónica de Transmisión , Neuronas/efectos de los fármacos , Obesidad/sangre , Obesidad/complicaciones , Proyectos Piloto , Cultivo Primario de Células , Multimerización de Proteína , Ratas , Pruebas de Toxicidad Aguda
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