ArticleNature2014
Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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
106 citing papers in PubMed, 251 citations in OpenAlex.
- Trial
- IDE-mediated GLP-1 degradation as the basis for designing long-acting and CNS-stable GLP-1 receptor agonists.Science advances · 2026Article
- Achieving protease substrate-specific inhibition by mAb dual functional selections.Protein science : a publication of the Protein Society · 2026Article
- Selective Inhibition of Insulin-Degrading Enzyme Eliminates Hemolysis Interference in Serum Insulin Measurements.Diagnostics (Basel, Switzerland) · 2026Article
- Article
- Spin-driven enantioselective regulation of cyclooxygenase-2 activity for rheumatoid arthritis therapy via chiral gold nanohelices.Nature communications · 2026Article
- It Takes Two to Tango: Current Understanding of the Role of M16 Family of Proteases and Their Structural Properties.Biomolecules · 2025Review
- Characterization and modulation of human insulin degrading enzyme conformational dynamics to control enzyme activity.bioRxiv : the preprint server for biology · 2025Article
- Decreased expression of insulin-degrading enzyme increases gluconeogenesis and glucose production in cultured hepatocytes administered with glucagon.Scientific reports · 2025Article
- Assessment of insulin-degrading enzyme inhibitor for the treatment of corneal erosion in a rat model.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Article
- The role of dysregulated copper metabolism in diabetes and its complications: a review.Frontiers in endocrinology · 2025Review
- Hepatic WDR23 proteostasis mediates insulin homeostasis by regulating insulin-degrading enzyme capacity.GeroScience · 2024Article
- Inflammation primes the murine kidney for recovery by activating AZIN1 adenosine-to-inosine editing.The Journal of clinical investigation · 2024Article
- Inhibition of insulin degrading enzyme suppresses osteoclast hyperactivity via enhancing Nrf2-dependent antioxidant response in glucocorticoid-induced osteonecrosis of the femoral head.Molecular medicine (Cambridge, Mass.) · 2024Article
- Article
- Type-2 Diabetes, Pancreatic Amylin, and Neuronal Metabolic Remodeling in Alzheimer's Disease.Molecular nutrition & food research · 2024Review
- Islet cell stress induced by insulin-degrading enzyme deficiency promotes regeneration and protection from autoimmune diabetes.iScience · 2024Article
- Investigating the potential of 6-substituted 3-formyl chromone derivatives as anti-diabetic agents using in silico methods.Scientific reports · 2024Article
- Inhibition of insulin-degrading enzyme in human neurons promotes amyloid-β deposition.Neuronal signaling · 2023Article
- The Insulin-Degrading Enzyme from Structure to Allosteric Modulation: New Perspectives for Drug Design.Biomolecules · 2023Review
46 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
Despite decades of speculation that inhibiting endogenous insulin degradation might treat type-2 diabetes, and the identification of IDE (insulin-degrading enzyme) as a diabetes susceptibility gene, the relationship between the activity of the zinc metalloprotein IDE and glucose homeostasis remains unclear. Although Ide(-/-) mice have elevated insulin levels, they exhibit impaired, rather than improved, glucose tolerance that may arise from compensatory insulin signalling dysfunction. IDE inhibitors that are active in vivo are therefore needed to elucidate IDE's physiological roles and to determine its potential to serve as a target for the treatment of diabetes. Here we report the discovery of a physiologically active IDE inhibitor identified from a DNA-templated macrocycle library. An X-ray structure of the macrocycle bound to IDE reveals that it engages a binding pocket away from the catalytic site, which explains its remarkable selectivity. Treatment of lean and obese mice with this inhibitor shows that IDE regulates the abundance and signalling of glucagon and amylin, in addition to that of insulin. Under physiological conditions that augment insulin and amylin levels, such as oral glucose administration, acute IDE inhibition leads to substantially improved glucose tolerance and slower gastric emptying. These findings demonstrate the feasibility of modulating IDE activity as a new therapeutic strategy to treat type-2 diabetes and expand our understanding of the roles of IDE in glucose and hormone regulation.
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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 Socratic graph.