ArticleCirculation research2012
Hyperamylinemia contributes to cardiac dysfunction in obesity and diabetes: a study in humans and rats.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 2 of them syntheses 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
87 citing papers in PubMed, 2 syntheses or guidelines pooled it, 134 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
- Amyloid Biomarkers in Conformational Diseases at Face Value: A Systematic Review.Molecules (Basel, Switzerland) · 2017Pooled it
- Trial
- Amyloid-Forming Amylin Secreted by the Pancreas Promotes Hypoxia-Inducible Factor Activation and Mitochondrial Alterations in Liver and Heart During Type 2 Diabetes Pathogenesis.Comprehensive physiology · 2026Article
- Cardiac remodelling in type 2 diabetes: Pathophysiological mechanisms and opportunities for multiscale computational modelling and simulation.The Journal of physiology · 2026Review
- Peripheral amylin modulation rebalances brain glycolysis and Tau-Ser214 phosphorylation via cAMP-PKA signaling.iScience · 2026Article
- The story of amylin: from physiology to therapy.Nature metabolism · 2026Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Calcium Signaling and Cardiac Adaptation to Stress: Focus on Pregnancy and Diabetes.Biomolecules · 2025Review
- Cardiac ageing: from hallmarks to therapeutic opportunities.Cardiovascular research · 2025Review
- Type 2 Diabetes Mellitus: A Metabolic Model of Accelerated Aging - Multi-Organ Mechanisms and Intervention Approaches.Aging and disease · 2025Review
- Proteostatic Imbalance Drives the Pathogenesis and Age-Related Exacerbation of Heart Failure With Preserved Ejection Fraction.JACC. Basic to translational science · 2025Article
- The role of amylin, a gut-brain axis hormone, in metabolic and neurological disorders.FASEB bioAdvances · 2025Review
- Neuroinflammation induced by amyloid-forming pancreatic amylin: Rationale for a mechanistic hypothesis.Biophysical chemistry · 2024Review
- Changes in hippocampal volume, synaptic plasticity and amylin sensitivity in an animal model of type 2 diabetes are associated with increased vulnerability to amyloid-beta in advancing age.Frontiers in aging neuroscience · 2024Article
- Skin capillary amylin deposition resembles brain amylin vasculopathy in rats.Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association · 2023Article
- Distinct Effects of Mitochondrial NaJournal of the American Heart Association · 2023Article
- Adiponectin and metabolic cardiovascular diseases: Therapeutic opportunities and challenges.Genes & diseases · 2023Review
- 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
27 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
8 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleHyperamylinemia is common in patients with obesity and insulin resistance, coincides with hyperinsulinemia, and results in amyloid deposition. Amylin amyloids are generally considered a pancreatic disorder in type 2 diabetes. However, elevated circulating levels of amylin may also lead to amylin accumulation and proteotoxicity in peripheral organs, including the heart.
objectiveTo test whether amylin accumulates in the heart of obese and type 2 diabetic patients and to uncover the effects of amylin accumulation on cardiac morphology and function. METHODS AND
resultsWe compared amylin deposition in failing and nonfailing hearts from lean, obese, and type 2 diabetic humans using immunohistochemistry and Western blots. We found significant accumulation of large amylin oligomers, fibrils, and plaques in failing hearts from obese and diabetic patients but not in normal hearts and failing hearts from lean, nondiabetic humans. Small amylin oligomers were even elevated in nonfailing hearts from overweight/obese patients, suggesting an early state of accumulation. Using a rat model of hyperamylinemia transgenic for human amylin, we observed that amylin oligomers attach to the sarcolemma, leading to myocyte Ca(2+) dysregulation, pathological myocyte remodeling, and diastolic dysfunction, starting from prediabetes. In contrast, prediabetic rats expressing the same level of wild-type rat amylin, a nonamyloidogenic isoform, exhibited normal heart structure and function.
conclusionsHyperamylinemia promotes amylin deposition in the heart, causing alterations of cardiac myocyte structure and function. We propose that detection and disruption of cardiac amylin buildup may be both a predictor of heart dysfunction and a novel therapeutic strategy in diabetic cardiomyopathy.
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.