O-GlcNAcylated p53 in the liver modulates hepatic glucose production

p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starv...

Descripción completa

Detalles Bibliográficos
Autores: González Rellán, María Jesús, Fernández Fondevila, Marcos, Fernández Paz, Uxía, Rodríguez Murueta-Goyena, Amaia, Varela Rey, Marta María, Veyrat-Durebex, Christelle, Seoane Ruzo, Samuel, Bernardo, Ganeko, Lopitz-Otsoa, Fernando, Fernández Ramos, David, Bilbao, Jon, Iglesias López, Cristina, Nóvoa Deaño, Eva María, Ameneiro Quiñoy, Cristina, Senra, Ana, Beiroa, Daniel, Cuñarro, Juan, Chantada Vazquez, María D.P., García Vence, María, Bravo López, Susana Belén, Silva Lima, Natalia Da, Porteiro Couto, Begoña, Carneiro Freire, Carmen, Vidal Figueroa, Anxo, Tovar Carro, Sulay A., Müller, Timo D., Ferno, Johan, Guallar Artal, Diana, Fidalgo Pérez, Miguel Ángel, Sabio, Guadalupe, Herzig, Stephan, Yang, Won Ho, Cho, Jin Won, Martínez Chantar, María Luz, Pérez Fernández, Román, López Pérez, Miguel A., Diéguez González, Carlos, Mato, José M., Millet, Óscar, Coppari, Roberto, Woodhoo, Ashwin, Fruhbeck, Gema, Nogueiras Pozo, Rubén
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/38735
Acceso en línea:https://hdl.handle.net/10347/38735
Access Level:acceso abierto
Palabra clave:Metabolic syndrome
Pre-diabetes
O-GlcNAcylated
p53
32 Ciencias médicas
Descripción
Sumario:p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis

Similares en LA Referencia