Author, as appears in the article.: 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;
Department: Ciències Mèdiques Bàsiques
URV's Author/s: Fernandez Veledo, Sonia
Keywords: cardiac hypertrophy g protein-coupled receptors grk2 heart failure high fat diet Activation Cardiac hypertrophy Dysfunction G protein-coupled receptors Grk2 Heart failure High fat diet Human heart Insulin resistance Interactome Mechanisms Metabolism Oxidative stress Phenotype Resistance
Abstract: 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.
Thematic Areas: Biochemistry Biochemistry & molecular biology Biophysics Biotecnología Cell biology Ciência de alimentos Ciências biológicas i Ciências biológicas ii Ciências biológicas iii Educação física Enfermagem Ensino Farmacia Materiais Medicina i Medicina ii Medicina iii Medicina veterinaria Molecular biology Molecular medicine Nutrição Química
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: sonia.fernandez@urv.cat
Author identifier: 0000-0003-2906-3788
Record's date: 2023-05-20
Papper version: info:eu-repo/semantics/acceptedVersion
Link to the original source: https://www.sciencedirect.com/science/article/pii/S0925443914002853?via%3Dihub
Papper original source: Biochimica Et Biophysica Acta-Molecular Basis Of Disease. 1842 (12): 2448-2456
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
Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/
Article's DOI: 10.1016/j.bbadis.2014.09.004
Entity: Universitat Rovira i Virgili
Journal publication year: 2014
Publication Type: Journal Publications
Repositori URV