Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes.
<h4>Background and aims</h4>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-ocur...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0237667 |
| _version_ | 1818675243173019648 |
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| author | Nelly F Altamirano-Bustamante Eulalia Garrido-Magaña Eugenia Morán Aurora Calderón Karina Pasten-Hidalgo Rosa Angélica Castillo-Rodríguez Gerardo Rojas Reyna Lara-Martínez Edgar Leyva-García Mateo Larralde-Laborde Guadalupe Domíguez Chiharu Murata Yolanda Margarita-Vazquez Rafael Payro Manuel Barbosa Alejandro Valderrama Hortencia Montesinos Alejandra Domínguez-Camacho Víctor H García-Olmos Regina Ferrer Patricia G Medina-Bravo Fernanda Santoscoy Cristina Revilla-Monsalve Luis Felipe Jiménez-García Julio Morán Jalil Villalobos-Alva Mario Javier Villalobos Raúl Calzada-León Perla Altamirano Myriam M Altamirano-Bustamante |
| author_facet | Nelly F Altamirano-Bustamante Eulalia Garrido-Magaña Eugenia Morán Aurora Calderón Karina Pasten-Hidalgo Rosa Angélica Castillo-Rodríguez Gerardo Rojas Reyna Lara-Martínez Edgar Leyva-García Mateo Larralde-Laborde Guadalupe Domíguez Chiharu Murata Yolanda Margarita-Vazquez Rafael Payro Manuel Barbosa Alejandro Valderrama Hortencia Montesinos Alejandra Domínguez-Camacho Víctor H García-Olmos Regina Ferrer Patricia G Medina-Bravo Fernanda Santoscoy Cristina Revilla-Monsalve Luis Felipe Jiménez-García Julio Morán Jalil Villalobos-Alva Mario Javier Villalobos Raúl Calzada-León Perla Altamirano Myriam M Altamirano-Bustamante |
| author_sort | Nelly F Altamirano-Bustamante |
| collection | DOAJ |
| description | <h4>Background and aims</h4>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.<h4>Materials and methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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. |
| first_indexed | 2024-12-17T08:24:29Z |
| format | Article |
| id | doaj.art-652cb12b4c944b90bca1b0fa52f7e6ce |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T08:24:29Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-652cb12b4c944b90bca1b0fa52f7e6ce2022-12-21T21:56:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01158e023766710.1371/journal.pone.0237667Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes.Nelly F Altamirano-BustamanteEulalia Garrido-MagañaEugenia MoránAurora CalderónKarina Pasten-HidalgoRosa Angélica Castillo-RodríguezGerardo RojasReyna Lara-MartínezEdgar Leyva-GarcíaMateo Larralde-LabordeGuadalupe DomíguezChiharu MurataYolanda Margarita-VazquezRafael PayroManuel BarbosaAlejandro ValderramaHortencia MontesinosAlejandra Domínguez-CamachoVíctor H García-OlmosRegina FerrerPatricia G Medina-BravoFernanda SantoscoyCristina Revilla-MonsalveLuis Felipe Jiménez-GarcíaJulio MoránJalil Villalobos-AlvaMario Javier VillalobosRaúl Calzada-LeónPerla AltamiranoMyriam M Altamirano-Bustamante<h4>Background and aims</h4>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.<h4>Materials and methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pone.0237667 |
| spellingShingle | Nelly F Altamirano-Bustamante Eulalia Garrido-Magaña Eugenia Morán Aurora Calderón Karina Pasten-Hidalgo Rosa Angélica Castillo-Rodríguez Gerardo Rojas Reyna Lara-Martínez Edgar Leyva-García Mateo Larralde-Laborde Guadalupe Domíguez Chiharu Murata Yolanda Margarita-Vazquez Rafael Payro Manuel Barbosa Alejandro Valderrama Hortencia Montesinos Alejandra Domínguez-Camacho Víctor H García-Olmos Regina Ferrer Patricia G Medina-Bravo Fernanda Santoscoy Cristina Revilla-Monsalve Luis Felipe Jiménez-García Julio Morán Jalil Villalobos-Alva Mario Javier Villalobos Raúl Calzada-León Perla Altamirano Myriam M Altamirano-Bustamante Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0237667 |
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