Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/21786
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Inhibition of PTP1B restores IRS1-mediated hepatic insulin signaling in IRS2-deficient mice |
Autor: | González-Rodríguez, Águeda CSIC ORCID; Mas, José A.; Sanz-González, Silvia M. CSIC; Ros, Manuel; Burks, Deborah J.; Valverde, Ángela M. CSIC ORCID | Palabras clave: | PTP1B restores Inhibition IRS1 IRS2 |
Fecha de publicación: | 22-nov-2009 | Editor: | American Diabetes Association | Citación: | Diabetes 59(3): 588-599 (2010) | Resumen: | [Objective]: Mice with complete deletion of insulin receptor substrate 2 (IRS2) develop hyperglycaemia, impaired hepatic insulin signaling and elevated gluconeogenesis, whereas mice deficient for protein tyrosine phosphatase (PTP) 1B display an opposing hepatic phenotype characterized by increased sensitivity to insulin. To define the relationship between these two signaling pathways in the regulation of liver metabolism, we used genetic and pharmacological approaches to study the effects of inhibiting PTP1B on hepatic insulin signaling and expression of gluconeogenic enzymes in IRS2−/− deficient mice. [Research design and methods]: We analyzed glucose homeostasis and insulin signaling in liver and isolated hepatocytes from IRS2−/− and IRS2−/−/PTP1B−/−. Additionally, hepatic insulin signaling was assessed in control and IRS2−/− mice treated with resveratrol, an anti-oxidant present in red wine. [Results]: In livers of hyperglycaemic IRS2−/− mice, the expression levels of PTP1B and its association with the insulin receptor (IR) were increased. The absence of PTP1B in the double mutant mice restored hepatic IRS1-mediated phosphatidylinositol (PI) 3-kinase/Akt/Foxo1 signaling. Moreover, resveratrol treatment of hyperglycaemic IRS2−/− mice decreased hepatic PTP1B mRNA and inhibited PTP1B activity, thereby restoring IRS1-mediated PI 3-kinase/Akt/Foxo1 signaling and peripheral insulin sensitivity. [Conclusions]: By regulating the phosphorylation state of IR, PTB1B determines sensitivity to insulin in liver and exerts a unique role in the interplay between IRS1 and IRS2 in the modulation of hepatic insulin action. | Versión del editor: | http://dx.doi.org/10.2337/db09-0796 | URI: | http://hdl.handle.net/10261/21786 | DOI: | 10.2337/db09-0796 | ISSN: | 0012-1797 |
Aparece en las colecciones: | (IIBM) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
irs2mice.pdf | 560,67 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
45
checked on 01-abr-2024
SCOPUSTM
Citations
104
checked on 11-abr-2024
WEB OF SCIENCETM
Citations
89
checked on 24-feb-2024
Page view(s)
514
checked on 18-abr-2024
Download(s)
303
checked on 18-abr-2024