ArticleJournal of cellular and molecular medicine2008
Transgenic mice overexpressing human G972R IRS-1 show impaired insulin action and insulin secretion.
Article in Journal of cellular and molecular medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status.Signal transduction and targeted therapy · 2025Review
- Mechanisms and therapeutics of insulin signaling transduction genes in diabetic cardiomyopathy: a comprehensive updated review.Frontiers in endocrinology · 2025Review
- Insulin signaling and its application.Frontiers in endocrinology · 2023Review
- Phase separation of insulin receptor substrate 1 drives the formation of insulin/IGF-1 signalosomes.Cell discovery · 2022Article
- Posttranscriptional Regulation of Insulin Resistance: Implications for Metabolic Diseases.Biomolecules · 2022Review
- A Missense Mutation in IRS1 is Associated with the Development of Early-Onset Type 2 Diabetes.International journal of endocrinology · 2020Article
- MicroRNAs as Regulators of Insulin Signaling: Research Updates and Potential Therapeutic Perspectives in Type 2 Diabetes.International journal of molecular sciences · 2018Review
- Pharmacogenetics of oral antidiabetes drugs: evidence for diverse signals at the IRS1 locus.The pharmacogenomics journal · 2018Article
- Insulin receptor signaling in normal and insulin-resistant states.Cold Spring Harbor perspectives in biology · 2014Review
- Individualized therapy for type 2 diabetes: clinical implications of pharmacogenetic data.Molecular diagnosis & therapy · 2012Review
- Article
- A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2012Article
- Unraveling pancreatic islet biology by quantitative proteomics.Expert review of proteomics · 2011Review
- Insulin-like growth factor axis gene polymorphisms and clinical outcomes in pancreatic cancer.Gastroenterology · 2010Article
- Enforced expression of protein kinase C in skeletal muscle causes physical inactivity, fatty liver and insulin resistance in the brain.Journal of cellular and molecular medicine · 2010Article
- Insulin signaling regulating genes: effect on T2DM and cardiovascular risk.Nature reviews. Endocrinology · 2009Review
- IRS1 G972R polymorphism and type 2 diabetes: a paradigm for the difficult ascertainment of the contribution to disease susceptibility of 'low-frequency-low-risk' variants.Diabetologia · 2009Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Molecular scanning of human insulin receptor substrate (Irs) genes revealed a single lrs1 prevalent variant, a glycine to arginine change at codon 972 (G972R); previous in vitro studies had demonstrated that the presence of this variant results in an impaired activation of the insulin signalling pathway, while human studies gave controversial results regarding its role in the pathogenesis of insulin resistance and related diseases. To address in vivo impact of this IRS-1 variant on whole body glucose homeostasis and insulin signalling, we have generated transgenic mice overexpressing it (Tg972) and evaluated insulin action in the liver, skeletal muscle and adipose tissue and assessed glucose homeostasis both under a normal diet and a high-fat diet. We found that Tg972 mice developed age-related glucose and insulin intolerance and hyperglycaemia, with insulin levels comparatively low. Glucose utilization and insulin signalling were impaired in all key insulin target tissues in Tg972 mice. There were no differences in pancreatic morphology between Tg972 and wild-type mice, however when insulin secretion was evaluated in isolated islets, it was significantly reduced in Tg972 mice islets at any glucose concentration tested. Under a high-fat diet, Tg972 mice had increased body and adipose tissue weight, and were more prone to develop diet-induced glucose and insulin intolerance. So, we believe that Tg972 mice may represent a useful model to elucidate the interaction between genetic and environmental factors in insulin resistance pathogenesis. Furthermore, they may become an important tool to test novel tailored therapies.
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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.