ArticleThe Journal of clinical investigation1996
A common amino acid polymorphism in insulin receptor substrate-1 causes impaired insulin signaling. Evidence from transfection studies.
Article in The Journal of clinical investigation, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 3 of them syntheses that pooled it.
What it found
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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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 3 syntheses or guidelines pooled it, 231 citations in OpenAlex.
- Pooled it
- Genetic variants associated with insulin signaling and glucose homeostasis in the pathogenesis of insulin resistance in polycystic ovary syndrome: a systematic review.Journal of assisted reproduction and genetics · 2013 · on this mapPooled it
- Gly972Arg variant in the insulin receptor substrate-1 gene and association with Type 2 diabetes: a meta-analysis of 27 studies.Diabetologia · 2003Pooled it
- Trial
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- Diabetes mellitus with severe insulin resistance in a young male patient with a heterozygous pathogenicClinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2024Article
- Phase separation of insulin receptor substrate 1 drives the formation of insulin/IGF-1 signalosomes.Cell discovery · 2022Article
- Insulin action at a molecular level - 100 years of progress.Molecular metabolism · 2021Review
- Genetic and Physiological Effects of Insulin on Human Urate Homeostasis.Frontiers in physiology · 2021Article
- Multifaceted Interweaving Between Extracellular Matrix, Insulin Resistance, and Skeletal Muscle.Cells · 2018Review
- Pharmacogenetics of oral antidiabetes drugs: evidence for diverse signals at the IRS1 locus.The pharmacogenomics journal · 2018Article
- Pharmacogenetics of posttransplant diabetes mellitus.The pharmacogenomics journal · 2017Review
- Lack of association between the insulin receptor substrates-1 Gly972Arg polymorphism and type-2 diabetes mellitus among Saudis from Eastern Saudi Arabia.Saudi medical journal · 2015Article
- Genetic association study between INSULIN pathway related genes and high myopia in a Han Chinese population.Molecular biology reports · 2015Article
- Causal drift, robust signaling, and complex disease.PloS one · 2015Article
- Joint effect of insulin signaling genes on all-cause mortality.Atherosclerosis · 2014Article
- Association of the genetic variants of insulin receptor substrate 1 (IRS-1) with type 2 diabetes mellitus in a Saudi population.Endocrine · 2014Article
- Article
- Insulin receptor signaling in normal and insulin-resistant states.Cold Spring Harbor perspectives in biology · 2014Review
- Joint effect of insulin signaling genes on insulin secretion and glucose homeostasis.The Journal of clinical endocrinology and metabolism · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Insulin receptor substrates-1 (IRS-1) is the major cytoplasmic substrate of the insulin and IGF-1 receptors. Recent studies have identified multiple sequence variants of IRS-1, especially in patients with non-insulin-dependent diabetes mellitus. In the present study, we have examined insulin-stimulated processes in 32D(IR) cells, a myeloid progenitor cell stably overexpressing the insulin receptor, transfected with wild-type human-IRS-1 or the most common human variant of IRS-1 in which glycine 972 is replaced by arginine. As compared to wild-type IRS-1, insulin stimulation of cells transfected with mutant IRS-1 exhibited a 32% decrease in incorporation of [3H]thymidine into DNA (P = 0.002), a 36% decrease in IRS-1 associated phosphatidylinositol (PI) 3-kinase activity (P = 0.004) and a 25% decrease in binding of the p85 regulatory subunit of PI 3-kinase to IRS-1 (P = 0.002). There was also a tendency for a decrease in Grb2 binding to IRS-1 and insulin-stimulated mitogen-activated protein kinase activity, however, these were not statistically significant. The changes occurred with no change in insulin receptor or IRS-1 tyrosine phosphorylation. These data indicate that the mutation in codon 972 in IRS-1 impairs insulin-stimulated signaling, especially along the PI 3-kinase pathway, and may contribute to insulin resistance in normal and diabetic populations.
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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.