ArticleDiabetes2014
Insulin inhibits cardiac contractility by inducing a Gi-biased β2-adrenergic signaling in hearts.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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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.
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Who cites it
49 citing papers in PubMed, 95 citations in OpenAlex.
- Intersecting Molecular Pathways in Cardiovascular Disease and Diabetes Mellitus: Emerging Roles of Inflammation and Therapeutics.Diabetes/metabolism research and reviews · 2026Review
- Inhibition of the upregulated phosphodiesterase 4D isoforms improves SERCA2a function in diabetic cardiomyopathy.British journal of pharmacology · 2025Article
- In-depth phosphoproteomic profiling of the insulin signaling response in heart tissue and cardiomyocytes unveils canonical and specialized regulation.Cardiovascular diabetology · 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
- Characterizing Adrenergic Regulation of Glucose Transporter 4-Mediated Glucose Uptake and Metabolism in the Heart.JACC. Basic to translational science · 2023Article
- Probing spatiotemporal PKA activity at the ryanodine receptor and SERCA2a nanodomains in cardomyocytes.Cell communication and signaling : CCS · 2022Article
- Acute effects of euglycemic-hyperinsulinemia on myocardial contractility in male mice.Physiological reports · 2022Article
- Insulin Receptors and Insulin Action in the Heart: The Effects of Left Ventricular Assist Devices.Biomolecules · 2022Review
- Role of the Autonomic Nervous System in the Hemodynamic Response to Hyperinsulinemia-Implications for Obesity and Insulin Resistance.Current diabetes reports · 2022Review
- Phenotype of higher post-load insulin response as a predictor of all-cause mortality and cardiovascular mortality in the Chinese non-diabetic population.Diabetology & metabolic syndrome · 2022Article
- 3D-Encoded DENSE MRI with Zonal Excitation for Quantifying Biventricular Myocardial Strain During a Breath-Hold.Cardiovascular engineering and technology · 2021Article
- Hyperinsulinemia blunts sympathetic vasoconstriction: a possible role of β-adrenergic activation.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Cardiac Energy Metabolism in Heart Failure.Circulation research · 2021Review
- It takes a village: lessons from collaborative science.The Journal of clinical investigation · 2021Article
- Review
- Basic Mechanisms of Diabetic Heart Disease.Circulation research · 2020Review
- Sustained Stimulation of βDiabetes, metabolic syndrome and obesity : targets and therapy · 2020Article
- Diabetes Increases the Vulnerability of the Cardiac Mitochondrial Network to Criticality.Frontiers in physiology · 2020Article
- Phosphodiesterase 5 Associates With β2 Adrenergic Receptor to Modulate Cardiac Function in Type 2 Diabetic Hearts.Journal of the American Heart Association · 2019Article
- βCirculation research · 2019Article
Corrections and comments
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Authors and funding
15 authors at 9 institutions in 2 countries.
Funding
Abstract
Insulin and adrenergic stimulation are two divergent regulatory systems that may interact under certain pathophysiological circumstances. Here, we characterized a complex consisting of insulin receptor (IR) and β2-adrenergic receptor (β2AR) in the heart. The IR/β2AR complex undergoes dynamic dissociation under diverse conditions such as Langendorff perfusions of hearts with insulin or after euglycemic-hyperinsulinemic clamps in vivo. Activation of IR with insulin induces protein kinase A (PKA) and G-protein receptor kinase 2 (GRK2) phosphorylation of the β2AR, which promotes β2AR coupling to the inhibitory G-protein, Gi. The insulin-induced phosphorylation of β2AR is dependent on IRS1 and IRS2. After insulin pretreatment, the activated β2AR-Gi signaling effectively attenuates cAMP/PKA activity after β-adrenergic stimulation in cardiomyocytes and consequently inhibits PKA phosphorylation of phospholamban and contractile responses in myocytes in vitro and in Langendorff perfused hearts. These data indicate that increased IR signaling, as occurs in hyperinsulinemic states, may directly impair βAR-regulated cardiac contractility. This β2AR-dependent IR and βAR signaling cross-talk offers a molecular basis for the broad interaction between these signaling cascades in the heart and other tissues or organs that may contribute to the pathophysiology of metabolic and cardiovascular dysfunction in insulin-resistant states.
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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.