ArticleFrontiers in molecular biosciences2020
Insulin-Regulated Aminopeptidase Inhibition Ameliorates Metabolism in Obese Zucker Rats.
Article in Frontiers in molecular biosciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Systematic review: pain, cognition, and cardioprotection-unpacking oxytocin's contributions in a sport context.Frontiers in physiology · 2024Pooled it
- Discovery of Novel Allosteric Inhibitor Hits for Insulin-Regulated Aminopeptidase Provides Insights on Enzymatic Mechanism.ACS omega · 2025Article
- Stabilization of the open conformation οf insulin-regulated aminopeptidase by a novel substrate-selective small-molecule inhibitor.Protein science : a publication of the Protein Society · 2024Article
- Fetal pancreas size and maternal serum biomarkers glycated albumin and insulin-regulated aminopeptidase provide no potential for early prediction of gestational diabetes mellitus.Archives of gynecology and obstetrics · 2023Observational
- The emerging multifunctional roles of ERAP1, ERAP2 and IRAP between antigen processing and renin-angiotensin system modulation.Frontiers in immunology · 2022Review
- Trehalose Ameliorates Diabetic Cardiomyopathy: Role of the PK2/PKR Pathway.Oxidative medicine and cellular longevity · 2021Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of our study was to determine the influence of inhibition of insulin-regulated aminopeptidase/oxytocinase (IRAP) on glucose tolerance and metabolism of skeletal muscle and visceral adipose tissue in obese Zucker rats. Obese Zucker rats administered with IRAP inhibitor-HFI-419 at a dose of 29 μg/100 g BW/day by osmotic minipumps implanted subcutaneously for 2 weeks. Two-hour intraperitoneal glucose tolerance test (ipGTT) was performed in fasting rats. Plasma oxytocin levels were measured by enzyme immunoassay after plasma extraction. In the musculus quadriceps and epididymal adipose tissue, the expression of factors affecting tissue oxidative status and metabolism was determined by real-time qPCR and/or Western blot analysys. The plasma and tissue enzymatic activities were determined by colorimetric or fluorometric method. Circulated oxytocin levels in obese animals strongly tended to increase after HFI-419 administration. This was accompanied by significantly improved glucose utilization during ipGTT and decreased area under the curve (AUC) for glucose. In skeletal muscle IRAP inhibitor treatment up-regulated enzymes of antioxidant defense system - superoxide dismutase 1 and 2 and improved insulin signal transduction pathway. HFI-419 increased skeletal muscle aminopeptidase A expression and activity and normalized its plasma levels in obese animals. In epididymal adipose tissue, gene expression of markers of inflammation and adipocyte hypertrophy was down-regulated in obese rats after HFI-419 treatment. Our results demonstrate that IRAP inhibition improves whole-body glucose tolerance in insulin-resistant Zucker fatty rats and that this metabolic effect of HFI-419 involves ameliorated redox balance in skeletal muscle.
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