Autor según el artículo: Lucas, Elisa; Jurado-Pueyo, Maria; Fortuno, Maria A.; Fernandez-Veledo, Sonia; Vila-Bedmar, Rocio; Jimenez-Borreguero, Luis J.; Lazcano, Juan J.; Gao, Ehre; Gomez-Ambrosi, Javier; Friuehbeck, Gema; Koch, Walter J.; Diez, Javier; Mayor, Federico, Jr.; Murga, Cristina;
Departamento: Ciències Mèdiques Bàsiques
Autor/es de la URV: Fernandez Veledo, Sonia
Palabras clave: Resistance Phenotype Oxidative stress Metabolism Mechanisms Interactome Insulin resistance Human heart High fat diet Heart failure Grk2 G protein-coupled receptors Dysfunction Cardiac hypertrophy Activation high fat diet heart failure grk2 g protein-coupled receptors cardiac hypertrophy
Resumen: G protein-coupled receptor kinase 2 (GRK2) has recently emerged as a negative modulator of insulin signaling. GRK2 downregulation improves insulin sensitivity and prevents systemic insulin resistance. Cardiac GRK2 levels are increased in human heart failure, while genetically inhibiting GRK2 leads to cardioprotection in mice. However, the molecular basis underlying the deleterious effects of GRK2 up-regulation and the beneficial effects of its inhibition in the heart are not fully understood. Therefore, we have explored the interconnections among a systemic insulin resistant status, GRK2 dosage and cardiac insulin sensitivity in adult (9 month-old) animals. GRK2(+/-) mice display enhanced cardiac insulin sensitivity and mild heart hypertrophy with preserved systolic function. Cardiac gene expression is reprogrammed in these animals, with increased expression of genes related to physiological hypertrophy, while the expression of genes related to pathological hypertrophy or to diabetes/obesity co-morbidities is repressed. Notably, we find that cardiac GRK2 levels increase in situations where insulin resistance develops, such as in ob/ob mice or after high fat diet feeding. Our data suggest that GRK2 downregulation/inhibition can help maintain cardiac function in the face of co-morbidities such as insulin resistance, diabetes or obesity by sustaining insulin sensitivity and promoting a gene expression reprogramming that confers cardioprotection. (C) 2014 Elsevier B.V. All rights reserved.
Áreas temáticas: Química Nutrição Molecular medicine Molecular biology Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Farmacia Ensino Enfermagem Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciência de alimentos Cell biology Biotecnología Biophysics Biochemistry & molecular biology Biochemistry
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
Direcció de correo del autor: sonia.fernandez@urv.cat
Identificador del autor: 0000-0003-2906-3788
Fecha de alta del registro: 2024-09-07
Versión del articulo depositado: info:eu-repo/semantics/acceptedVersion
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Biochimica Et Biophysica Acta-Molecular Basis Of Disease. 1842 (12): 2448-2456
Referencia de l'ítem segons les normes APA: Lucas, Elisa; Jurado-Pueyo, Maria; Fortuno, Maria A.; Fernandez-Veledo, Sonia; Vila-Bedmar, Rocio; Jimenez-Borreguero, Luis J.; Lazcano, Juan J.; Gao, (2014). Downregulation of G protein-coupled receptor kinase 2 levels enhances cardiac insulin sensitivity and switches on cardioprotective gene expression patterns. Biochimica Et Biophysica Acta-Molecular Basis Of Disease, 1842(12), 2448-2456. DOI: 10.1016/j.bbadis.2014.09.004
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2014
Tipo de publicación: Journal Publications
Repositori URV