ArticleCirculation2011
G protein-coupled receptor kinase 2 activity impairs cardiac glucose uptake and promotes insulin resistance after myocardial ischemia.
Article in Circulation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.
- Triglyceride-glucose index and heart failure: a systematic review and meta-analysis.Cardiovascular diabetology · 2023Pooled it
- Effect of SGLT-2 inhibitor, dapagliflozin, on left ventricular remodeling in patients with type 2 diabetes and HFrEF.BMC cardiovascular disorders · 2023Trial
- Beyond β-Adrenergic Receptor Brake: Compartment-Selective GRK2 Programs from Heart Failure to Cardio-Oncology.Kinases and phosphatases · 2026Article
- Low-dose esmolol attenuates sepsis-induced myocardial injury: association with improved autophagic homeostasis and PI3K/Akt signaling.Journal of intensive care · 2026Article
- Role of circadian rhythms in heart failure: insights from myocardial energy metabolism.Journal of translational medicine · 2025Review
- GRK2 and Mitochondrial Dynamics in Cardiovascular Health and Disease.International journal of molecular sciences · 2025Review
- Canonical or non-canonical, all aspects of G protein-coupled receptor kinase 2 in heart failure.Acta physiologica (Oxford, England) · 2025Review
- Therapeutic Efficacy of a Novel Pharmacologic GRK2 Inhibitor in Multiple Animal Models of Heart Failure.JACC. Basic to translational science · 2025Article
- Hepatic-vascular crosstalk via GRK2: fenofibrate improves endothelial function by restoring lipid metabolism and NO signaling in obese mice.Frontiers in physiology · 2025Article
- Unraveling the RKIP-YY1 axis: immune crosstalk in the pathogenesis of metabolic disorders.Frontiers in immunology · 2025Review
- Relationship of the trajectory of the triglyceride-glucose index with heart failure: the Kailuan study.Lipids in health and disease · 2024Article
- Gene expression and ultra-structural evidence for metabolic derangement in the primary mitral regurgitation heart.European heart journal open · 2024Article
- Dysfunctional mitochondria elicit bioenergetic decline in the aged heart.The journal of cardiovascular aging · 2024Article
- Resolution of insulin resistance, lactic acidosis, and decrease in mechanical support requirements in patients post orthotopic heart transplant with the use of long-acting insulin glargine.Journal of cardiothoracic surgery · 2024Article
- Role of G protein-coupled receptor kinases (GRKs) in βPharmacology research & perspectives · 2024Article
- A cardiac amino-terminal GRK2 peptide inhibits insulin resistance yet enhances maladaptive cardiovascular and brown adipose tissue remodeling in females during diet-induced obesity.Journal of molecular and cellular cardiology · 2023Review
- Association between the triglyceride-glucose index and the risk of mortality among patients with chronic heart failure: results from a retrospective cohort study in China.Cardiovascular diabetology · 2023Article
- Characterizing Adrenergic Regulation of Glucose Transporter 4-Mediated Glucose Uptake and Metabolism in the Heart.JACC. Basic to translational science · 2023Article
- Novel roles for G protein-coupled receptor kinases in cardiac injury and repair.Biochemical Society transactions · 2023Review
- Branched-Chain Amino Acid Metabolism in the Failing Heart.Cardiovascular drugs and therapy · 2023Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAlterations in cardiac energy metabolism downstream of neurohormonal stimulation play a crucial role in the pathogenesis of heart failure. The chronic adrenergic stimulation that accompanies heart failure is a signaling abnormality that leads to the upregulation of G protein-coupled receptor kinase 2 (GRK2), which is pathological in the myocyte during disease progression in part owing to uncoupling of the β-adrenergic receptor system. In this study, we explored the possibility that enhanced GRK2 expression and activity, as seen during heart failure, can negatively affect cardiac metabolism as part of its pathogenic profile. METHODS AND
resultsPositron emission tomography studies revealed in transgenic mice that cardiac-specific overexpression of GRK2 negatively affected cardiac metabolism by inhibiting glucose uptake and desensitization of insulin signaling, which increases after ischemic injury and precedes heart failure development. Mechanistically, GRK2 interacts with and directly phosphorylates insulin receptor substrate-1 in cardiomyocytes, causing insulin-dependent negative signaling feedback, including inhibition of membrane translocation of the glucose transporter GLUT4. This identifies insulin receptor substrate-1 as a novel nonreceptor target for GRK2 and represents a new pathological mechanism for this kinase in the failing heart. Importantly, inhibition of GRK2 activity prevents postischemic defects in myocardial insulin signaling and improves cardiac metabolism via normalized glucose uptake, which appears to participate in GRK2-targeted prevention of heart failure.
conclusionsOur data provide novel insights into how GRK2 is pathological in the injured heart. Moreover, it appears to be a critical mechanistic link within neurohormonal crosstalk governing cardiac contractile signaling/function through β-adrenergic receptors and metabolism through the insulin receptor.
Indexed as
Identifiers
What OpenQuestion holds
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.