The Effects of Aging on Male Mouse Pancreatic β-Cell Function Involve Multiple Events in the Regulation of Secretion: Influence of Insulin Sensitivity
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Título: | The Effects of Aging on Male Mouse Pancreatic β-Cell Function Involve Multiple Events in the Regulation of Secretion: Influence of Insulin Sensitivity |
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Autor/es: | Tudurí, Eva | Soriano, Sergi | Almagro, Lucía | García-Heredia, Anabel | Rafacho, Alex | Alonso Magdalena, Paloma | Nadal, Ángel | Quesada, Iván |
Grupo/s de investigación o GITE: | Fisiología Neuroendocrina (FINE) |
Centro, Departamento o Servicio: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología |
Palabras clave: | Pancreatic β-cell | Aging | Insulin secretion | KATP channels | Ca2+ signalling |
Área/s de conocimiento: | Fisiología |
Fecha de publicación: | 25-sep-2021 |
Editor: | Oxford University Press |
Cita bibliográfica: | The Journals of Gerontology: Series A. 2022, 77(3): 405-415. https://doi.org/10.1093/gerona/glab276 |
Resumen: | Aging is associated with a decline in peripheral insulin sensitivity and an increased risk of impaired glucose tolerance and type 2 diabetes. During conditions of reduced insulin sensitivity, pancreatic β-cells undergo adaptive responses to increase insulin secretion and maintain euglycemia. However, the existence and nature of β-cell adaptations and/or alterations during aging are still a matter of debate. In this study, we investigated the effects of aging on β-cell function from control (3-month-old) and aged (20-month-old) mice. Aged animals were further categorized in two groups: high insulin sensitive (aged-HIS) and low insulin sensitive (aged-LIS). Aged-LIS mice were hyperinsulinemic, glucose intolerant and displayed impaired glucose-stimulated insulin and C-peptide secretion, whereas aged-HIS animals showed characteristics in glucose homeostasis similar to controls. In isolated β-cells, we observed that glucose-induced inhibition of KATP channel activity was reduced with aging, particularly in the aged-LIS group. Glucose-induced islet NAD(P)H production was decreased in aged mice, suggesting impaired mitochondrial function. In contrast, voltage-gated Ca 2+ currents were higher in aged-LIS β-cells, and pancreatic islets of both aged groups displayed increased glucose-induced Ca 2+ signaling and augmented insulin secretion compared with controls. Morphological analysis of pancreas sections also revealed augmented β-cell mass with aging, especially in the aged-LIS group, as well as ultrastructural β-cell changes. Altogether, these findings indicate that aged mouse β-cells compensate for the aging-induced alterations in the stimulus-secretion coupling, particularly by adjusting their Ca 2+ influx to ensure insulin secretion. These results also suggest that decreased peripheral insulin sensitivity exacerbates the effects of aging on β-cells. |
Patrocinador/es: | This research was supported by grants from the Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación, Fondo Europeo de Desarrollo Regional (FEDER) and Generalitat Valenciana (BFU2017-86579-R and PROMETEO/2020/006 to AN and BFU2016-77125-R to IQ) and from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (grant No. 304388/2020-3 to AR) and the Programa Institucional de Internacionalização from the Coordenação de Aperfeiçoamento de pessoal de Nível Superior (CAPES). CIBERDEM is an initiative of the Instituto de Salud Carlos III. |
URI: | http://hdl.handle.net/10045/118386 |
ISSN: | 1079-5006 (Print) | 1758-535X (Online) |
DOI: | 10.1093/gerona/glab276 |
Idioma: | eng |
Tipo: | info:eu-repo/semantics/article |
Derechos: | © The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America |
Revisión científica: | si |
Versión del editor: | https://doi.org/10.1093/gerona/glab276 |
Aparece en las colecciones: | INV - NEUROVIS - Artículos de Revistas INV - FINE - Artículos de Revistas |
Archivos en este ítem:
Archivo | Descripción | Tamaño | Formato | |
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Tuduri_etal_2021_JGerontologySeriesA_accepted.pdf | Accepted Manuscript (acceso abierto) | 1,26 MB | Adobe PDF | Abrir Vista previa |
Tuduri_etal_2021_JGerontologySeriesA_final.pdf | Versión final (acceso restringido) | 8,74 MB | Adobe PDF | Abrir Solicitar una copia |
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