ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 217 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
217 citing papers in PubMed, 2 syntheses or guidelines pooled it, 483 citations in OpenAlex.
- IRS-2 rs1805097 polymorphism is associated with the decreased risk of colorectal cancer.Oncotarget · 2017Pooled it
- Association between insulin receptor substrate 1 Gly972Arg polymorphism and cancer risk.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Pooled it
- Zebrafish knockout models of atxn1a, atxn1b, and atxn1l reveal distinct and shared phenotypic and transcriptomic alterations.Human molecular genetics · 2026Article
- Insulin Regulates AKT/GSK-3β Signalling, Tau Phosphorylation, and Redox Homeostasis in SH-SY5Y Neuroblastoma Cells.International journal of molecular sciences · 2026Article
- Metabolic dysfunction and insulin resistance across major dementias: A comprehensive narrative review of the TyG index as a predictive marker.Metabolism open · 2026Review
- Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease.bioRxiv : the preprint server for biology · 2026Article
- Progranulin deficiency in the brain activates an insulin signaling pathway that may promote neurodegeneration.iScience · 2026Article
- Pharmacological modulation of the PI3K/AKT/GSK3β axis: a new frontier in Alzheimer's disease treatment.Inflammopharmacology · 2026Review
- Regulatory Genomic Circuitry of Brain Age by Integrative Functional Genomic Analyses.Genomics, proteomics & bioinformatics · 2025Article
- Novel differentially expressed genes and multiple biological pathways for Alzheimer's disease identified in brain tissue from African American donors.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Understanding the Intersection Between Hormonal Dynamics and Brain Plasticity in Alzheimer's Disease: A Narrative Review for Implementing New Therapeutic Strategies.Health science reports · 2025Review
- Progressive Alcohol-Related Brain Atrophy and White Matter Pathology Are Linked to Long-Term Inhibitory Effects on mTOR Signaling.Biomolecules · 2025Article
- The Novel Lipid Emulsion Vegaven Is Well Tolerated and Elicits Distinct Biological Actions Compared With a Mixed-Oil Lipid Emulsion Containing Fish Oil: A Parenteral Nutrition Trial in Piglets.The Journal of nutrition · 2025Article
- Associations Between Diabetes Mellitus and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Exploring the role of insulin resistance in bridging the metabolic syndrome and Alzheimer's disease-a review of mechanistic studies.Frontiers in endocrinology · 2025Review
- The effect of intra-nasal co-treatment with insulin and growth factor-rich serum on behavioral defects, hippocampal oxidative-nitrosative stress, and histological changes induced by icv-STZ in a rat model.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Insulin-like growth factor binding protein-2 in at-risk adults and autopsy-confirmed Alzheimer brains.Brain : a journal of neurology · 2024Article
- Potential molecular mechanism of exercise reversing insulin resistance and improving neurodegenerative diseases.Frontiers in physiology · 2024Review
- New insights toward molecular and nanotechnological approaches to antidiabetic agents for Alzheimer's disease.Molecular and cellular biochemistry · 2023Review
- Triglyceride-glucose index as a valuable predictor for aged 65-years and above in critical delirium patients: evidence from a multi-center study.BMC geriatrics · 2023Article
157 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Insulin resistance and diabetes might promote neurodegenerative disease, but a molecular link between these disorders is unknown. Many factors are responsible for brain growth, patterning, and survival, including the insulin-insulin-like growth factor (IGF)-signaling cascades that are mediated by tyrosine phosphorylation of insulin receptor substrate (IRS) proteins. Irs2 signaling mediates peripheral insulin action and pancreatic beta-cell function, and its failure causes diabetes in mice. In this study, we reveal two important roles for Irs2 signaling in the mouse brain. First, disruption of the Irs2 gene reduced neuronal proliferation during development by 50%, which dissociated brain growth from Irs1-dependent body growth. Second, neurofibrillary tangles containing phosphorylated tau accumulated in the hippocampus of old Irs2 knock-out mice, suggesting that Irs2 signaling is neuroprotective. Thus, dysregulation of the Irs2 branch of the insulin-Igf-signaling cascade reveals a molecular link between diabetes and neurodegenerative disease.
Indexed as
Identifiers
12904469PMC6740672W1508589930What OpenQuestion holds
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.