ArticleMetabolism: clinical and experimental2020
Hepatic insulin-degrading enzyme regulates glucose and insulin homeostasis in diet-induced obese mice.
Article in Metabolism: clinical and experimental, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Review
- 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
- Hyperglucagonemia and glucagon hypersecretion in early type 2 diabetes result from multifaceted dysregulation of pancreatic mouse α-cells.Pflugers Archiv : European journal of physiology · 2025Article
- Metabolic phenotypes in a Lyz2Cre recombinase mouse model.Frontiers in immunology · 2025Article
- Insights into circulating CEACAM1 in insulin clearance and disease progression: Evidence from the Portuguese PREVADIAB2 study.European journal of clinical investigation · 2024Article
- Hepatic WDR23 proteostasis mediates insulin homeostasis by regulating insulin-degrading enzyme capacity.GeroScience · 2024Article
- The Insulin-Degrading Enzyme from Structure to Allosteric Modulation: New Perspectives for Drug Design.Biomolecules · 2023Review
- Feeding during hibernation shifts gene expression toward active season levels in brown bears (Physiological genomics · 2023Article
- Molecular Genetics of Abnormal Redox Homeostasis in Type 2 Diabetes Mellitus.International journal of molecular sciences · 2023Review
- Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge.International journal of molecular sciences · 2022Article
- Insulin-degrading enzyme ablation in mouse pancreatic alpha cells triggers cell proliferation, hyperplasia and glucagon secretion dysregulation.Diabetologia · 2022Article
- Exploring the determinants of ethnic differences in insulin clearance between men of Black African and White European ethnicity.Acta diabetologica · 2022Article
- Article
- Amelioration of Age-Related Multiple Neuronal Impairments and Inflammation in High-Fat Diet-Fed Rats: The Prospective Multitargets of Geraniol.Oxidative medicine and cellular longevity · 2022Article
- Insects as a New Complex Model in Hormonal Basis of Obesity.International journal of molecular sciences · 2021Review
- Article
- Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
The insulin-degrading enzyme (IDE) is a metalloendopeptidase with a high affinity for insulin. Human genetic polymorphisms in Ide have been linked to increased risk for T2DM. In mice, hepatic Ide ablation causes glucose intolerance and insulin resistance when mice are fed a regular diet.
objectiveThese studies were undertaken to further investigate its regulatory role in glucose homeostasis and insulin sensitivity in diet-induced obesity.
methodsTo this end, we have compared the metabolic effects of loss versus gain of IDE function in mice fed a high-fat diet (HFD).
resultsWe demonstrate that loss of IDE function in liver (L-IDE-KO mouse) exacerbates hyperinsulinemia and insulin resistance without changes in insulin clearance but in parallel to an increase in pancreatic β-cell function. Insulin resistance was associated with increased FoxO1 activation and a ~2-fold increase of GLUT2 protein levels in the liver of HFD-fed mice in response to an intraperitoneal injection of insulin. Conversely, gain of IDE function (adenoviral delivery) improves glucose tolerance and insulin sensitivity, in parallel to a reciprocal ~2-fold reduction in hepatic GLUT2 protein levels. Furthermore, in response to insulin, IDE co-immunoprecipitates with the insulin receptor in liver lysates of mice with adenoviral-mediated liver overexpression of IDE.
conclusionsWe conclude that IDE regulates hepatic insulin action and whole-body glucose metabolism in diet-induced obesity via insulin receptor levels.
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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.