ArticleThe Journal of clinical investigation2020
Cardioprotective GLP-1 metabolite prevents ischemic cardiac injury by inhibiting mitochondrial trifunctional protein-α.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 76 citations in OpenAlex.
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- Discovery of a snail hibernation-inducer offering hibernation-like cardioprotection through metabolic rewiring and autophagy in mice.Nature communications · 2026Article
- Ambrisentan attenuates cisplatin-related mitochondrial dysfunction in the heart via regulation of p53 and NF-κB signaling.Scientific reports · 2026Article
- Abnormal Lipid Signaling Characterizes Diastolic Dysfunction in Pediatric Cardiomyopathy.JACC. Basic to translational science · 2026Article
- Glucagon-like Peptide-1 Receptor Dependent Signaling in Cardiovascular Health and Disease: A Mini-review.Journal of cardiovascular translational research · 2026Review
- GLP-1 and the cardiovascular system.The Journal of clinical investigation · 2026Review
- Metabo-epigenetic circuits of heart failure: chromatin-modifying enzymes as determinants of metabolic plasticity.EMBO molecular medicine · 2026Review
- Engineered GLP-1R-targeting nanoplatforms: multimodal therapeutics in human diseases.Journal of nanobiotechnology · 2025Review
- Current Perspectives on GLP-1 Agonists in Contemporary Clinical Practice from Science and Mechanistic Foundations To Optimal Translation.Current atherosclerosis reports · 2025Review
- Modern antidiabetic therapy by sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and dipeptidyl peptidase 4 inhibitors against cardiovascular diseases.Pharmacological reviews · 2025Review
- GLP-1 receptor agonists show no detrimental effect on sperm quality in mouse models and cell lines.Endocrine · 2025Article
- The Potential Role of GLP1-RAs Against Anticancer-Drug Cardiotoxicity: A Scoping Review.Journal of clinical medicine · 2025Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Investigating the impact of intestinal glucagon-like peptide-1 on hypoglycemia in type 1 diabetes.World journal of diabetes · 2025Article
- Emerging Mechanistic Insights and Therapeutic Strategies for Pulmonary Arterial Hypertension: A Focus on Right Ventricular Dysfunction and Novel Treatment Pathways.Biomedicines · 2025Review
- Glucagon-Like Peptide-1 Links Ingestion, Homeostasis, and the Heart.Comprehensive Physiology · 2025Review
- Increased oxidative phosphorylation through pyruvate dehydrogenase kinase 2 deficiency ameliorates cartilage degradation in mice with surgically induced osteoarthritis.Experimental & molecular medicine · 2025Article
- Glucagon-like Peptide-1 Receptor Agonists in Heart Failure: Mechanisms, Evidence and Identifying Optimal Candidates.Cardiac failure review · 2025Review
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Mechanisms mediating the cardioprotective actions of glucagon-like peptide 1 (GLP-1) were unknown. Here, we show in both ex vivo and in vivo models of ischemic injury that treatment with GLP-1(28-36), a neutral endopeptidase-generated (NEP-generated) metabolite of GLP-1, was as cardioprotective as GLP-1 and was abolished by scrambling its amino acid sequence. GLP-1(28-36) enters human coronary artery endothelial cells (caECs) through macropinocytosis and acts directly on mouse and human coronary artery smooth muscle cells (caSMCs) and caECs, resulting in soluble adenylyl cyclase Adcy10-dependent (sAC-dependent) increases in cAMP, activation of protein kinase A, and cytoprotection from oxidative injury. GLP-1(28-36) modulates sAC by increasing intracellular ATP levels, with accompanying cAMP accumulation lost in sAC-/- cells. We identify mitochondrial trifunctional protein-α (MTPα) as a binding partner of GLP-1(28-36) and demonstrate that the ability of GLP-1(28-36) to shift substrate utilization from oxygen-consuming fatty acid metabolism toward oxygen-sparing glycolysis and glucose oxidation and to increase cAMP levels is dependent on MTPα. NEP inhibition with sacubitril blunted the ability of GLP-1 to increase cAMP levels in coronary vascular cells in vitro. GLP-1(28-36) is a small peptide that targets novel molecular (MTPα and sAC) and cellular (caSMC and caEC) mechanisms in myocardial ischemic injury.
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