ReviewDiabetologia2012
Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2.
Review in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 541 papers, 2 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
541 citing papers in PubMed, 2 syntheses or guidelines pooled it, 973 citations in OpenAlex.
- Cellular and Molecular Pathophysiology of Gestational Diabetes.International journal of molecular sciences · 2024Pooled it
- The crucial role and mechanism of insulin resistance in metabolic disease.Frontiers in endocrinology · 2023Pooled it
- Serum fibrinogen-like protein 2 is associated with diabetic nephropathy severity and modulates high glucose-induced tubular dysfunction via Akt-FoxO1 signaling.Renal failure · 2026Article
- Insulin resistance in the 21st century: new takes on an old problem-2025 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetologia · 2026Review
- A hypothalamus-liver-skeletal muscle axis controlled by JNK1 and FGF21 mediates olanzapine-induced insulin resistance in an intraperitoneal treatment in male mice.Redox biology · 2026Article
- Review
- Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1.Nature communications · 2026Article
- Review
- SRM-Mediated Spermidine Synthesis Links Lipid Overload With AMPK Pathway to Regulate Hepatic Insulin Signaling and Gluconeogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Article
- The Complex Relation of Branched-Chain Amino Acids and Inflammation in the Obesity and Diabetes Context.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Acute amyloid-β exposure disrupts insulin signaling in hCMEC/D3 blood-brain barrier endothelial cells.Fluids and barriers of the CNS · 2026Article
- Insulin Resistance as a Systemic Metabolic Risk State for Cancer: Mechanisms, Biomarkers, and Prevention.International journal of molecular sciences · 2026Review
- Endurance training mitigates obesity-induced hippocampal impairment by enhancing neurotrophin signalling, synaptic plasticity, and cellular responses in a female rat model.IBRO neuroscience reports · 2026Article
- Review
- Metabolic dysfunction-associated steatotic liver disease: pathogenesis and novel treatment options.Molecular biomedicine · 2026Review
- Identification of a novel oral potential multiple agonist for obesity treatment: multi-target in silico study.Journal of computer-aided molecular design · 2026Article
- An engineered insulin analog with dual insulin and IGF-1 receptor agonism and distinct signaling.Science advances · 2026Article
- Progranulin deficiency in the brain activates an insulin signaling pathway that may promote neurodegeneration.iScience · 2026Article
- Article
481 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
2 authors at 1 institution in 1 country.
Funding
Abstract
The insulin receptor substrate proteins IRS1 and IRS2 are key targets of the insulin receptor tyrosine kinase and are required for hormonal control of metabolism. Tissues from insulin-resistant and diabetic humans exhibit defects in IRS-dependent signalling, implicating their dysregulation in the initiation and progression of metabolic disease. However, IRS1 and IRS2 are regulated through a complex mechanism involving phosphorylation of >50 serine/threonine residues (S/T) within their long, unstructured tail regions. In cultured cells, insulin-stimulated kinases (including atypical PKC, AKT, SIK2, mTOR, S6K1, ERK1/2 and ROCK1) mediate feedback (autologous) S/T phosphorylation of IRS, with both positive and negative effects on insulin sensitivity. Additionally, insulin-independent (heterologous) kinases can phosphorylate IRS1/2 under basal conditions (AMPK, GSK3) or in response to sympathetic activation and lipid/inflammatory mediators, which are present at elevated levels in metabolic disease (GRK2, novel and conventional PKCs, JNK, IKKβ, mPLK). An emerging view is that the positive/negative regulation of IRS by autologous pathways is subverted/co-opted in disease by increased basal and other temporally inappropriate S/T phosphorylation. Compensatory hyperinsulinaemia may contribute strongly to this dysregulation. Here, we examine the links between altered patterns of IRS S/T phosphorylation and the emergence of insulin resistance and diabetes.
Indexed as
Identifiers
What 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.