Cargando…
Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes
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 β-cell damage is evident. Here we wanted to investigate the level of naturally-ocurring or real (not s...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446879/ https://www.ncbi.nlm.nih.gov/pubmed/32833960 http://dx.doi.org/10.1371/journal.pone.0237667 |
_version_ | 1783574207390547968 |
---|---|
author | Altamirano-Bustamante, Nelly F. Garrido-Magaña, Eulalia Morán, Eugenia Calderón, Aurora Pasten-Hidalgo, Karina Castillo-Rodríguez, Rosa Angélica Rojas, Gerardo Lara-Martínez, Reyna Leyva-García, Edgar Larralde-Laborde, Mateo Domíguez, Guadalupe Murata, Chiharu Margarita-Vazquez, Yolanda Payro, Rafael Barbosa, Manuel Valderrama, Alejandro Montesinos, Hortencia Domínguez-Camacho, Alejandra García-Olmos, Víctor H. Ferrer, Regina Medina-Bravo, Patricia G. Santoscoy, Fernanda Revilla-Monsalve, Cristina Jiménez-García, Luis Felipe Morán, Julio Villalobos-Alva, Jalil Villalobos, Mario Javier Calzada-León, Raúl Altamirano, Perla Altamirano-Bustamante, Myriam M. |
author_facet | Altamirano-Bustamante, Nelly F. Garrido-Magaña, Eulalia Morán, Eugenia Calderón, Aurora Pasten-Hidalgo, Karina Castillo-Rodríguez, Rosa Angélica Rojas, Gerardo Lara-Martínez, Reyna Leyva-García, Edgar Larralde-Laborde, Mateo Domíguez, Guadalupe Murata, Chiharu Margarita-Vazquez, Yolanda Payro, Rafael Barbosa, Manuel Valderrama, Alejandro Montesinos, Hortencia Domínguez-Camacho, Alejandra García-Olmos, Víctor H. Ferrer, Regina Medina-Bravo, Patricia G. Santoscoy, Fernanda Revilla-Monsalve, Cristina Jiménez-García, Luis Felipe Morán, Julio Villalobos-Alva, Jalil Villalobos, Mario Javier Calzada-León, Raúl Altamirano, Perla Altamirano-Bustamante, Myriam M. |
author_sort | Altamirano-Bustamante, Nelly F. |
collection | PubMed |
description | 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 β-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 β-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 β-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 β-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. |
format | Online Article Text |
id | pubmed-7446879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-74468792020-08-26 Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes Altamirano-Bustamante, Nelly F. Garrido-Magaña, Eulalia Morán, Eugenia Calderón, Aurora Pasten-Hidalgo, Karina Castillo-Rodríguez, Rosa Angélica Rojas, Gerardo Lara-Martínez, Reyna Leyva-García, Edgar Larralde-Laborde, Mateo Domíguez, Guadalupe Murata, Chiharu Margarita-Vazquez, Yolanda Payro, Rafael Barbosa, Manuel Valderrama, Alejandro Montesinos, Hortencia Domínguez-Camacho, Alejandra García-Olmos, Víctor H. Ferrer, Regina Medina-Bravo, Patricia G. Santoscoy, Fernanda Revilla-Monsalve, Cristina Jiménez-García, Luis Felipe Morán, Julio Villalobos-Alva, Jalil Villalobos, Mario Javier Calzada-León, Raúl Altamirano, Perla Altamirano-Bustamante, Myriam M. PLoS One Research Article 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 β-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 β-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 β-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 β-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. Public Library of Science 2020-08-24 /pmc/articles/PMC7446879/ /pubmed/32833960 http://dx.doi.org/10.1371/journal.pone.0237667 Text en © 2020 Altamirano-Bustamante et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Altamirano-Bustamante, Nelly F. Garrido-Magaña, Eulalia Morán, Eugenia Calderón, Aurora Pasten-Hidalgo, Karina Castillo-Rodríguez, Rosa Angélica Rojas, Gerardo Lara-Martínez, Reyna Leyva-García, Edgar Larralde-Laborde, Mateo Domíguez, Guadalupe Murata, Chiharu Margarita-Vazquez, Yolanda Payro, Rafael Barbosa, Manuel Valderrama, Alejandro Montesinos, Hortencia Domínguez-Camacho, Alejandra García-Olmos, Víctor H. Ferrer, Regina Medina-Bravo, Patricia G. Santoscoy, Fernanda Revilla-Monsalve, Cristina Jiménez-García, Luis Felipe Morán, Julio Villalobos-Alva, Jalil Villalobos, Mario Javier Calzada-León, Raúl Altamirano, Perla Altamirano-Bustamante, Myriam M. Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes |
title | Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes |
title_full | Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes |
title_fullStr | Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes |
title_full_unstemmed | Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes |
title_short | Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes |
title_sort | protein-conformational diseases in childhood: naturally-occurring hiapp amyloid-oligomers and early β-cell damage in obesity and diabetes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446879/ https://www.ncbi.nlm.nih.gov/pubmed/32833960 http://dx.doi.org/10.1371/journal.pone.0237667 |
work_keys_str_mv | AT altamiranobustamantenellyf proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT garridomaganaeulalia proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT moraneugenia proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT calderonaurora proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT pastenhidalgokarina proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT castillorodriguezrosaangelica proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT rojasgerardo proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT laramartinezreyna proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT leyvagarciaedgar proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT larraldelabordemateo proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT domiguezguadalupe proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT muratachiharu proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT margaritavazquezyolanda proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT payrorafael proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT barbosamanuel proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT valderramaalejandro proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT montesinoshortencia proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT dominguezcamachoalejandra proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT garciaolmosvictorh proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT ferrerregina proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT medinabravopatriciag proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT santoscoyfernanda proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT revillamonsalvecristina proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT jimenezgarcialuisfelipe proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT moranjulio proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT villalobosalvajalil proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT villalobosmariojavier proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT calzadaleonraul proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT altamiranoperla proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes AT altamiranobustamantemyriamm proteinconformationaldiseasesinchildhoodnaturallyoccurringhiappamyloidoligomersandearlybcelldamageinobesityanddiabetes |