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Cardioprotective effect of genetic ablation of the G-protein-coupled receptor kinase GRK2 in adult pancreatic β-cells during high-fat diet
Journal article   Open access   Peer reviewed

Cardioprotective effect of genetic ablation of the G-protein-coupled receptor kinase GRK2 in adult pancreatic β-cells during high-fat diet

Jonathan Snyder, Chun-sun Jiang, Ran Hee Choi, Taylor Morgan, Jeffrey Roman, Lilly Underwood, Anna Maria Lucchese, Sarah Montgomery, Laurel A. Grisanti, Nicolai Doliba, …
The Journal of biological chemistry, v 301(4), 108388
01 Apr 2025
PMID: 40054692
url
https://doi.org/10.1016/j.jbc.2025.108388View
Published, Version of Record (VoR) Open

Abstract

glucose GRK2 islet Diabetes Heart Insulin Obesity
Cardiovascular diseases are a major comorbidity factor in patients with type 2 diabetes and a leading cause of death among them. Yet, mechanistically, how impairment in pancreatic islets alters cardiac function under different metabolic states remains largely unknown. Here, we investigate the role of the G-protein-coupled receptor kinase 2 (GRK2) in regulating islet adaptations to an obesogenic diet and its impact on myocardial function. Using a novel inducible β-cell-specific GRK2 knockout mouse model (βGRK2KO), we establish that loss of adult β-cell GRK2 delays metabolic islet maladaptation, protecting the heart against obesity-induced cardiac dysfunction. βGRK2KO are more insulin-sensitive than control mice and have improved cardiac function and myocardial morphology. Thus, genetic ablation of GRK2 in adult β-cells during an obesogenic diet play a cardioprotective role. This study prompts a novel therapeutic window for GRK2 intervention strategies for diabetic patients prone to cardiac dysfunction.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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