ArticleMetabolism: clinical and experimental2018
Liver-specific ablation of insulin-degrading enzyme causes hepatic insulin resistance and glucose intolerance, without affecting insulin clearance in mice.
Article in Metabolism: clinical and experimental, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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.
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Who cites it
36 citing papers in PubMed, 67 citations in OpenAlex.
- Glucocorticoid rhythm disruption drives hyperinsulinaemia in mice through beta cell glucocorticoid receptor signalling.bioRxiv : the preprint server for biology · 2026Article
- The physiology of MASLD: molecular pathways between liver and adipose tissues.Clinical science (London, England : 1979) · 2025Review
- Understanding the Insulin-Degrading Enzyme: A New Look at Alzheimer's Disease and Aβ Plaque Management.International journal of molecular sciences · 2025Review
- Unraveling novel mechanisms of ATP-Binding cassette (ABC) transporter in insulin Resistance-induced amyloidogenesis.Metabolic brain disease · 2025Review
- Decreased expression of insulin-degrading enzyme increases gluconeogenesis and glucose production in cultured hepatocytes administered with glucagon.Scientific reports · 2025Article
- Hepatic WDR23 proteostasis mediates insulin homeostasis by regulating insulin-degrading enzyme capacity.GeroScience · 2024Article
- Article
- Islet cell stress induced by insulin-degrading enzyme deficiency promotes regeneration and protection from autoimmune diabetes.iScience · 2024Article
- The Insulin-Degrading Enzyme from Structure to Allosteric Modulation: New Perspectives for Drug Design.Biomolecules · 2023Review
- Long-Term High-Fat Diet Decreases Renal Insulin-Degrading Enzyme Expression and Function by Inhibiting the PPARγ Pathway.Molecular nutrition & food research · 2023Article
- Article
- Altered serotonin metabolism in Takeda G protein-coupled receptor 5 knockout mice protects against diet-induced hepatic fibrosis.Liver research (Beijing, China) · 2022Article
- New Insights on the Regulation of the Insulin-Degrading Enzyme: Role of microRNAs and RBPs.Cells · 2022Article
- Regulation of Insulin Clearance by Non-Esterified Fatty Acids.Biomedicines · 2022Review
- Insulin-degrading enzyme ablation in mouse pancreatic alpha cells triggers cell proliferation, hyperplasia and glucagon secretion dysregulation.Diabetologia · 2022Article
- Proteomic analysis reveals exercise training induced remodelling of hepatokine secretion and uncovers syndecan-4 as a regulator of hepatic lipid metabolism.Molecular metabolism · 2022Article
- Review
- Exploring the determinants of ethnic differences in insulin clearance between men of Black African and White European ethnicity.Acta diabetologica · 2022Article
- The Physiology of Insulin Clearance.International journal of molecular sciences · 2022Review
- Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The role of insulin-degrading enzyme (IDE), a metalloprotease with high affinity for insulin, in insulin clearance remains poorly understood.
objectiveThis study aimed to clarify whether IDE is a major mediator of insulin clearance, and to define its role in the etiology of hepatic insulin resistance.
methodsWe generated mice with liver-specific deletion of Ide (L-IDE-KO) and assessed insulin clearance and action.
resultsL-IDE-KO mice exhibited higher (~20%) fasting and non-fasting plasma glucose levels, glucose intolerance and insulin resistance. This phenotype was associated with ~30% lower plasma membrane insulin receptor levels in liver, as well as ~55% reduction in insulin-stimulated phosphorylation of the insulin receptor, and its downstream signaling molecules, AKT1 and AKT2 (reduced by ~40%). In addition, FoxO1 was aberrantly distributed in cellular nuclei, in parallel with up-regulation of the gluconeogenic genes Pck1 and G6pc. Surprisingly, L-IDE-KO mice showed similar plasma insulin levels and hepatic insulin clearance as control mice, despite reduced phosphorylation of the carcinoembryonic antigen-related cell adhesion molecule 1, which upon its insulin-stimulated phosphorylation, promotes receptor-mediated insulin uptake to be degraded.
conclusionIDE is not a rate-limiting regulator of plasma insulin levels in vivo.
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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.