ArticleJournal of gastroenterology2018
Hepatic IRS1 and ß-catenin expression is associated with histological progression and overt diabetes emergence in NAFLD patients.
Article in Journal of gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- The crucial role and mechanism of insulin resistance in metabolic disease.Frontiers in endocrinology · 2023Pooled it
- γ-GC mitigates MASLD by reducing CD36 palmitoylation and plasma membrane translocation mediated by AKT/KLF10/zDHHC7 axis.Nutrition & metabolism · 2026Article
- Review on the Relationship Between TyG Index and CVD Incidence in Patients With T2DM With NAFLD.International journal of endocrinology · 2026Review
- LIMA1 O-GlcNAcylation Promotes Hepatic Lipid Deposition through Inducing β-catenin-Regulated FASn Expression in Metabolic Dysfunction-Associated Steatotic Liver Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver.Cell reports. Medicine · 2024Article
- Exploring the Multifaceted Landscape of MASLD: A Comprehensive Synthesis of Recent Studies, from Pathophysiology to Organoids and Beyond.Biomedicines · 2024Review
- Role and Regulation of Wnt/β-Catenin in Hepatic Perivenous Zonation and Physiological Homeostasis.The American journal of pathology · 2022Review
- Role of Insulin Resistance in MAFLD.International journal of molecular sciences · 2021Review
- Association Between Diabetes Mellitus and All-Cause and Cardiovascular Mortality Among Individuals With Ultrasound-Defined Non-Alcoholic Fatty Liver Disease.Frontiers in endocrinology · 2021Article
- The Role of Insulin Resistance and Diabetes in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2020Review
- Hepatic FATP5 expression is associated with histological progression and loss of hepatic fat in NAFLD patients.Journal of gastroenterology · 2020Article
- New Perspectives on Genetic Prediction for Pediatric Metabolic Associated Fatty Liver Disease.Frontiers in pediatrics · 2020Review
- The Intricate Relationship between Type 2 Diabetes Mellitus (T2DM), Insulin Resistance (IR), and Nonalcoholic Fatty Liver Disease (NAFLD).Journal of diabetes research · 2020Review
- Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism.Nature communications · 2019Article
Corrections and comments
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Authors and funding
24 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes. Our aim was to investigate the relationship between NAFLD and impaired glucose metabolism in terms of insulin receptor substrate 1 and 2 (IRS1 and IRS2) expression in the liver.
methodsLiver biopsy was performed at the University of Tokyo Hospital between November 2011 and March 2016 on 146 patients with NAFLD who were not being treated with any diabetes or dyslipidemia drugs. Among them, 63 underwent liver biopsy after an overnight fast, and 83 at 5 h after an oral glucose tolerance test (OGTT). Differences in messenger RNA (mRNA) levels of several glucose metabolism-related factors were determined and correlated with hepatic histological changes assessed by NAFLD activity score. We prospectively followed up with the patients until May 2017.
resultsHepatic necroinflammation was significantly correlated with serum insulin levels and inversely correlated with IRS1 mRNA levels. In specimens obtained after an OGTT, hepatic necroinflammation and IRS1 expression correlated significantly with both peripheral and hepatic insulin resistance. We also found that hepatic β-catenin and glucokinase mRNA levels were elevated in patients undergoing liver biopsy after an OGTT, especially in those with less hepatic necroinflammation and a lower degree of fibrosis. A prospective cohort study showed that ballooning is the most significant risk factor for developing diabetes.
conclusionsThe decreased hepatic expression of IRS1 and β-catenin in NAFLD is linked to histological progression such as ballooning, and might lead to diabetes as a result of impaired glucose metabolism.
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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 OpenQuestion graph.