ArticleCellular signalling2015
Insulin induces IRS2-dependent and GRK2-mediated β2AR internalization to attenuate βAR signaling in cardiomyocytes.
Article in Cellular signalling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Inhibition of the upregulated phosphodiesterase 4D isoforms improves SERCA2a function in diabetic cardiomyopathy.British journal of pharmacology · 2025Article
- Canonical or non-canonical, all aspects of G protein-coupled receptor kinase 2 in heart failure.Acta physiologica (Oxford, England) · 2025Review
- Role of G protein-coupled receptor kinases (GRKs) in βPharmacology research & perspectives · 2024Article
- Insulin signaling in the heart.American journal of physiology. Endocrinology and metabolism · 2021Review
- Review
- Paroxetine Attenuates Cardiac Hypertrophy Via Blocking GRK2 and ADRB1 Interaction in Hypertension.Journal of the American Heart Association · 2021Article
- Adipose TBX1 regulates β-adrenergic sensitivity in subcutaneous adipose tissue and thermogenic capacity in vivo.Molecular metabolism · 2020Article
- DSCAM-AS1 mediates pro-hypertrophy role of GRK2 in cardiac hypertrophy aggravation via absorbing miR-188-5p.In vitro cellular & developmental biology. Animal · 2020Article
- Phosphodiesterase 5 Associates With β2 Adrenergic Receptor to Modulate Cardiac Function in Type 2 Diabetic Hearts.Journal of the American Heart Association · 2019Article
- Of mice and men: models and mechanisms of diabetic cardiomyopathy.Basic research in cardiology · 2018Review
- Functionally distinct and selectively phosphorylated GPCR subpopulations co-exist in a single cell.Nature communications · 2018Article
- New Insights in Cardiac β-Adrenergic Signaling During Heart Failure and Aging.Frontiers in pharmacology · 2018Review
- Cross-Talk Between Insulin Signaling and G Protein-Coupled Receptors.Journal of cardiovascular pharmacology · 2017Review
- Insulin and β Adrenergic Receptor Signaling: Crosstalk in Heart.Trends in endocrinology and metabolism: TEM · 2017Review
- High-fat diet induces protein kinase A and G-protein receptor kinase phosphorylation of βThe Journal of physiology · 2017Article
- Inhibiting Insulin-Mediated β2-Adrenergic Receptor Activation Prevents Diabetes-Associated Cardiac Dysfunction.Circulation · 2017Article
- Article
- Cardiovascular Dysfunction Following Burn Injury: What We Have Learned from Rat and Mouse Models.International journal of molecular sciences · 2016Review
- Trafficking of β-Adrenergic Receptors: Implications in Intracellular Receptor Signaling.Progress in molecular biology and translational science · 2015Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The counter-regulatory effects of insulin and catecholamines on carbohydrate and lipid metabolism are well studied, whereas the details of insulin regulation of β adrenergic receptor (βAR) signaling pathway in heart remain unknown. Here, we characterize a novel signaling pathway of insulin receptor (IR) to G protein-coupled receptor kinase 2 (GRK2) in the heart. Insulin stimulates recruitment of GRK2 to β2AR, which induces β2AR phosphorylation at the GRK sites of serine 355/356 and subsequently β2AR internalization. Insulin thereby suppresses βAR-induced cAMP-PKA activities and contractile response in neonatal and adult mouse cardiomyocytes. Deletion of insulin receptor substrate 2 (IRS2) disrupts the complex of IR and GRK2, which attenuates insulin-mediated β2AR phosphorylation at the GRK sites and β2AR internalization, and the counter-regulation effects of insulin on βAR signaling. These data indicate the requirements of IRS2 and GRK2 for insulin to stimulate counter-regulation of βAR via β2AR phosphorylation and internalization in cardiomyocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.