ArticleJournal of the American Heart Association2014
Cardioprotection by controlling hyperamylinemia in a "humanized" diabetic rat model.
Article in Journal of the American Heart Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Circulating Amyloid and Misfolded Biomarkers in Early Myocardial Injury: A Systematic Review and Epistemic Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- Combined training and hormones/enzymes with insulinotropic actions in individuals with overweight and type 2 diabetes mellitus: A randomized controlled trial.European journal of sport science · 2024Trial
- From Adipose Dysfunction to Multi-Organ Steatosis: Defining the Metabolic Steatotic Axis.Current issues in molecular biology · 2026Review
- Synthetic deformylated α-helical PSMα3 as a selective inhibitor of human amyloid aggregation.Scientific reports · 2025Article
- Calcium Signaling and Cardiac Adaptation to Stress: Focus on Pregnancy and Diabetes.Biomolecules · 2025Review
- Distinct Effects of Mitochondrial NaJournal of the American Heart Association · 2023Article
- Mammalian models of diabetes mellitus, with a focus on type 2 diabetes mellitus.Nature reviews. Endocrinology · 2023Review
- The association between renal accumulation of pancreatic amyloid-forming amylin and renal hypoxia.Frontiers in endocrinology · 2023Review
- Linking hIAPP misfolding and aggregation with type 2 diabetes mellitus: a structural perspective.Bioscience reports · 2022Review
- Gestational diabetes triggers postpartum cardiac hypertrophy via activation of calcineurin/NFAT signaling.Scientific reports · 2021Article
- Rosmarinic Acid Potently Detoxifies Amylin Amyloid and Ameliorates Diabetic Pathology in a Transgenic Rat Model of Type 2 Diabetes.ACS pharmacology & translational science · 2021Article
- Amylin Dyshomeostasis Hypothesis: Small Vessel-Type Ischemic Stroke in the Setting of Type-2 Diabetes.Stroke · 2021Review
- Amylin deposition activates HIF1α and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) signaling in failing hearts of non-human primates.Communications biology · 2021Article
- β-Hairpin Peptide Mimics Decrease Human Islet Amyloid Polypeptide (hIAPP) Aggregation.Frontiers in cell and developmental biology · 2021Article
- Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease.Frontiers in molecular neuroscience · 2020Review
- Diabetic microcirculatory disturbances and pathologic erythropoiesis are provoked by deposition of amyloid-forming amylin in red blood cells and capillaries.Kidney international · 2020Article
- Lower sarcoplasmic reticulum CaHeart rhythm · 2019Article
- The receptor for advanced glycation endproducts is a mediator of toxicity by IAPP and other proteotoxic aggregates: Establishing and exploiting common ground for novel amyloidosis therapies.Protein science : a publication of the Protein Society · 2018Review
- Computational modeling of amylin-induced calcium dysregulation in rat ventricular cardiomyocytes.Cell calcium · 2018Article
- Amylin and diabetic cardiomyopathy - amylin-induced sarcolemmal CaBiochimica et biophysica acta. Molecular basis of disease · 2018Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundChronic hypersecretion of the pancreatic hormone amylin is common in humans with obesity or prediabetic insulin resistance and induces amylin aggregation and proteotoxicity in the pancreas. We recently showed that hyperamylinemia also affects the cardiovascular system. Here, we investigated whether amylin aggregates interact directly with cardiac myocytes and whether controlling hyperamylinemia protects the heart. METHODS AND
resultsBy Western blot, we found abundant amylin aggregates in lysates of cardiac myocytes from obese patients, but not in controls. Aggregated amylin was elevated in failing hearts, suggesting a role in myocyte injury. Using rats overexpressing human amylin in the pancreas (HIP rats) and control myocytes incubated with human amylin, we show that amylin aggregation at the sarcolemma induces oxidative stress and Ca(2+) dysregulation. In time, HIP rats developed cardiac hypertrophy and left-ventricular dilation. We then tested whether metabolites with antiaggregation properties, such as eicosanoid acids, limit myocardial amylin deposition. Rats were treated with an inhibitor of soluble epoxide hydrolase, the enzyme that degrades endogenous eicosanoids. Treatment doubled the blood concentration of eicosanoids, which drastically reduced incorporation of aggregated amylin in cardiac myocytes and blood cells, without affecting pancreatic amylin secretion. Animals in the treated group showed reduced cardiac hypertrophy and left-ventricular dilation. The cardioprotective mechanisms included the mitigation of amylin-induced cardiac oxidative stress and Ca(2+) dysregulation.
conclusionsThe results suggest blood amylin as a novel therapeutic target in diabetic heart disease and elevating blood levels of antiaggregation metabolites as a pharmacological strategy to reduce amylin aggregation and amylin-mediated cardiotoxicity.
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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.