Universidad de Burgos Repositorio Repositorio
Por favor, use este identificador para citar o enlazar este ítem: http://hdl.handle.net/10259/4965

Ver estadísticas de uso
Título : Liver-specific ablation of insulin-degrading enzyme causes hepatic insulin resistance and glucose intolerance, without affecting insulin clearance in mice
Autor : Villa Pérez, Pablo .
Merino, Beatriz .
Fernández Díaz, Cristina M. .
Cidad, Pilar .
Lobatón, Carmen D. .
Moreno, Alfredo .
Muturi, Harrison T. .
Ghadieh, Hilda E. .
Najjar, Sonia M. .
Leissring, Malcolm A. .
Cózar Castellano, Irene .
Perdomo Hernández, Germán M.
Publicado en: Metabolism. 2018, V. 88, p. 1-11
Editorial : Elsevier
Fecha de publicación : nov-2018
ISSN : 0026-0495
DOI: 10.1016/j.metabol.2018.08.001
Resumen : The role of insulin-degrading enzyme (IDE), a metalloprotease with high affinity for insulin, in insulin clearance remains poorly understood. OBJECTIVE: This study aimed to clarify whether IDE is a major mediator of insulin clearance, and to define its role in the etiology of hepatic insulin resistance. Methods We generated mice with liver-specific deletion of Ide (L-IDE-KO) and assessed insulin clearance and action. Results L-IDE-KO mice exhibited higher (~20%) fasting and non-fasting plasma glucose levels, glucose intolerance and insulin resistance. This phenotype was associated with ~30% lower plasma membrane insulin receptor levels in liver, as well as ~55% reduction in insulin-stimulated phosphorylation of the insulin receptor, and its downstream signaling molecules, AKT1 and AKT2 (reduced by ~40%). In addition, FoxO1 was aberrantly distributed in cellular nuclei, in parallel with up-regulation of the gluconeogenic genes Pck1 and G6pc. Surprisingly, L-IDE-KO mice showed similar plasma insulin levels and hepatic insulin clearance as control mice, despite reduced phosphorylation of the carcinoembryonic antigen-related cell adhesion molecule 1, which upon its insulin-stimulated phosphorylation, promotes receptor-mediated insulin uptake to be degraded. Conclusion IDE is not a rate-limiting regulator of plasma insulin levels in vivo
Palabras clave: nsulin-degrading enzyme
Hepatic insulin resistance
Insulin recepto
Carcinoembryonic antigen-related cell adhesion molecule 1
Materia: Endocrinología
Endocrinology
Licencia: https://creativecommons.org/licenses/by/4.0/
URI : http://hdl.handle.net/10259/4965
Versión del editor: https://doi.org/10.1016/j.metabol.2018.08.001
Aparece en las colecciones: Artículos DIABO-TER

Ficheros en este ítem:

Fichero Descripción Tamaño Formato
Villa-Metabolism_2018.pdf1,37 MBAdobe PDFVisualizar/Abrir

Este ítem está sujeto a una licencia Creative Commons Licencia Creative Commons
Creative Commons

Los ítems del Repositorio Institucional de la Universidad de Burgos están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.

 

Valid XHTML 1.0! DSpace Software Copyright © 2002-2008 MIT and Hewlett-Packard - Sobre DSpace