ArticlePloS one2015
Cardioprotection Resulting from Glucagon-Like Peptide-1 Administration Involves Shifting Metabolic Substrate Utilization to Increase Energy Efficiency in the Rat Heart.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 55 citations in OpenAlex.
- Exenatide and glucagon co-infusion increases myocardial glucose uptake and improves markers of diastolic dysfunction in adults with type 2 diabetes.Scientific reports · 2025Trial
- Effect of liraglutide on myocardial glucose uptake and blood flow in stable chronic heart failure patients: A double-blind, randomized, placebo-controlled LIVE sub-study.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2019Trial
- Combination GLP-1 and Insulin Treatment Fails to Alter Myocardial Fuel Selection vs. Insulin Alone in Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2018Trial
- A systematic review and meta-analyses of glucagon-like peptide-1 receptor agonists in acute myocardial infarction.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2026Review
- Potential Relationship Between YTHDF3 and CFTR in Myocardial Ischemia-Reperfusion Injury.Journal of cellular and molecular medicine · 2026Article
- Role of GLP‑1 receptor agonists in sepsis and their therapeutic potential in sepsis‑induced muscle atrophy (Review).International journal of molecular medicine · 2025Review
- GLP-1 Receptor Agonists and Myocardial Perfusion: Bridging Mechanisms to Clinical Outcomes.International journal of molecular sciences · 2025Review
- Semaglutide Improves Myocardial Perfusion and Performance in a Large Animal Model of Coronary Artery Disease.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- The role of protein O-GlcNAcylation in diabetic cardiomyopathy.Biochemical Society transactions · 2024Review
- GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms.The Journal of endocrinology · 2024Review
- The impact of glucagon-like peptide-1 receptor agonists in the patients undergoing anesthesia or sedation: systematic review and meta-analysis.Perioperative medicine (London, England) · 2024Article
- Underlying mechanisms and cardioprotective effects of SGLT2i and GLP-1Ra: insights from cardiovascular magnetic resonance.Cardiovascular diabetology · 2024Review
- Advances in Metabolic Remodeling and Intervention Strategies in Heart Failure.Journal of cardiovascular translational research · 2024Review
- Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action.Nature reviews. Cardiology · 2023Review
- Glucagon and exenatide improve contractile recovery following ischaemia/reperfusion in the isolated perfused rat heart.Physiological reports · 2023Article
- Discrepancy between the Actions of Glucagon-like Peptide-1 Receptor Ligands in the Protection of the Heart against Ischemia Reperfusion Injury.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Glucagon-like peptide-1 (GLP-1) receptor agonists and their cardiovascular benefits-The role of the GLP-1 receptor.British journal of pharmacology · 2022Review
- GLP-1 Receptor: A New Target for Sepsis.Frontiers in pharmacology · 2021Review
- Cardioprotective GLP-1 metabolite prevents ischemic cardiac injury by inhibiting mitochondrial trifunctional protein-α.The Journal of clinical investigation · 2020Article
- Effects of Liraglutide on Myocardial Function After Cardiac Surgery: A Secondary Analysis of the Randomised Controlled GLOBE Trial.Journal of clinical medicine · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous studies have shown that glucagon-like peptide-1 (GLP-1) provides cardiovascular benefits independent of its role on peripheral glycemic control. However, the precise mechanism(s) by which GLP-1 treatment renders cardioprotection during myocardial ischemia remain unresolved. Here we examined the role for GLP-1 treatment on glucose and fatty acid metabolism in normal and ischemic rat hearts following a 30 min ischemia and 24 h reperfusion injury, and in isolated cardiomyocytes (CM). Relative carbohydrate and fat oxidation levels were measured in both normal and ischemic hearts using a 1-13C glucose clamp coupled with NMR-based isotopomer analysis, as well as in adult rat CMs by monitoring pH and O2 consumption in the presence of glucose or palmitate. In normal heart, GLP-1 increased glucose uptake (↑64%, p<0.05) without affecting glycogen levels. In ischemic hearts, GLP-1 induced metabolic substrate switching by increasing the ratio of carbohydrate versus fat oxidation (↑14%, p<0.01) in the LV area not at risk, without affecting cAMP levels. Interestingly, no substrate switching occurred in the LV area at risk, despite an increase in cAMP (↑106%, p<0.05) and lactate (↑121%, p<0.01) levels. Furthermore, in isolated CMs GLP-1 treatment increased glucose utilization (↑14%, p<0.05) and decreased fatty acid oxidation (↓15%, p<0.05) consistent with in vivo finding. Our results show that this benefit may derive from distinct and complementary roles of GLP-1 treatment on metabolism in myocardial sub-regions in response to this injury. In particular, a switch to anaerobic glycolysis in the ischemic area provides a compensatory substrate switch to overcome the energetic deficit in this region in the face of reduced tissue oxygenation, whereas a switch to more energetically favorable carbohydrate oxidation in more highly oxygenated remote regions supports maintaining cardiac contractility in a complementary manner.
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