ArticleThe Journal of clinical investigation2018
RAGE binds preamyloid IAPP intermediates and mediates pancreatic β cell proteotoxicity.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis 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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Host insulin resistance caused byFrontiers in cellular and infection microbiology · 2023Pooled it
- Potential for anti‑angiogenic therapy targeting the receptor for advanced glycation end products/VEGF axis in ulcerative colitis (Review).Molecular medicine reports · 2026Review
- Dietary bioactive compounds targeting insulin resistance: mechanisms and preventive potential.Frontiers in nutrition · 2026Review
- Effect of Copper-Catalyzed Oxidation on the Aggregation of the Islet Amyloid Polypeptide.Antioxidants (Basel, Switzerland) · 2025Article
- Amylin: emergent therapeutic opportunities in overweight, obesity and diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- Peripheral Inflammation and Insulin Resistance: Their Impact on Blood-Brain Barrier Integrity and Glia Activation in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Advanced Glycation End Products in Disease Development and Potential Interventions.Antioxidants (Basel, Switzerland) · 2025Review
- Repurposing major metabolites of lamiaceae family as potential inhibitors ofFrontiers in pharmacology · 2025Article
- Sensing danger in the islet: the roles of pattern recognition receptors in β cells and type 1 diabetes.Frontiers in immunology · 2025Review
- Role of the Receptor for Advanced Glycation End Products (RAGE) and Its Ligands in Inflammatory Responses.Biomolecules · 2024Review
- Understanding the structural dynamics of human islet amyloid polypeptide: Advancements in and applications of ion-mobility mass spectrometry.Biophysical chemistry · 2024Review
- Differential effects of ganglioside lipids on the conformation and aggregation of islet amyloid polypeptide.Protein science : a publication of the Protein Society · 2024Article
- Neuroinflammation induced by amyloid-forming pancreatic amylin: Rationale for a mechanistic hypothesis.Biophysical chemistry · 2024Review
- The processing intermediate of human amylin, pro-amylin(1-48), has in vivo and in vitro bioactivity.Biophysical chemistry · 2024Article
- RIPK3 promotes islet amyloid-induced β-cell loss and glucose intolerance in a humanized mouse model of type 2 diabetes.Molecular metabolism · 2024Article
- Non-fibril form but not fibril form of human islet amyloid polypeptide 8-20 changes brain functions in mice.PloS one · 2024Article
- A pancreatic player in dementia: pathological role for islet amyloid polypeptide accumulation in the brain.Neural regeneration research · 2023Review
- Review
- Gender Differences in Insulin Resistance: New Knowledge and Perspectives.Current issues in molecular biology · 2023Review
- Alpha cell receptor for advanced glycation end products associate with glucagon expression in type 1 diabetes.Scientific reports · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid polypeptide (IAPP) in pancreatic islets, resulting in β cell toxicity, which exacerbates type 2 diabetes and islet transplant failure. It is not fully clear how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or treated. We recently defined the properties of toxic IAPP species. Here, we have identified a receptor-mediated mechanism of islet amyloidosis-induced proteotoxicity. In human diabetic pancreas and in cellular and mouse models of islet amyloidosis, increased expression of the receptor for advanced glycation endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) β cell and islet inflammation, toxicity, and apoptosis. RAGE selectively bound toxic intermediates, but not nontoxic forms of h-IAPP, including amyloid fibrils. The isolated extracellular ligand-binding domains of soluble RAGE (sRAGE) blocked both h-IAPP toxicity and amyloid formation. Inhibition of the interaction between h-IAPP and RAGE by sRAGE, RAGE-blocking antibodies, or genetic RAGE deletion protected pancreatic islets, β cells, and smooth muscle cells from h-IAPP-induced inflammation and metabolic dysfunction. sRAGE-treated h-IAPP Tg mice were protected from amyloid deposition, loss of β cell area, β cell inflammation, stress, apoptosis, and glucose intolerance. These findings establish RAGE as a mediator of IAPP-induced toxicity and suggest that targeting the IAPP/RAGE axis is a potential strategy to mitigate this source of β cell dysfunction in metabolic disease.
Indexed as
Identifiers
What Socratic 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 Socratic graph.