ArticleCardiovascular research2015
Loss of the insulin receptor in murine megakaryocytes/platelets causes thrombocytosis and alterations in IGF signalling.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
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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
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- The impact of triglyceride-glucose index on ischemic stroke: a systematic review and meta-analysis.Cardiovascular diabetology · 2023Pooled it
- Association between triglyceride glucose index and risk of cerebrovascular disease: systematic review and meta-analysis.Cardiovascular diabetology · 2022Pooled it
- Effect of insulin resistance on ticagrelor-versus clopidogrel-based dual antiplatelet therapy for secondary prevention of stroke in carriers ofCMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2026Trial
- Outcomes of endovascular thrombectomy in acute ischemic stroke patients with insulin resistance.Journal of neurointerventional surgery · 2026Article
- Association between metabolic score for insulin resistance and future stroke risk in patients with cardiovascular-kidney-metabolic syndrome stages 0-3: a longitudinal analysis based on CHARLS.Cardiovascular diabetology · 2025Article
- The triglyceride-glucose index: updating evidence from clinical settings to molecular mechanisms in ageing-related cerebrovascular diseases.Cardiovascular diabetology · 2025Review
- Prognostic value of triglyceride-glucose index combined with stress hyperglycemia ratio for all-cause mortality in critically ill patients with stroke.Cardiovascular diabetology · 2025Article
- Linking Triglyceride-Glucose Index to Spontaneous Intracerebral Hemorrhage: Mechanisms and Predictive Insights.Medical science monitor : international medical journal of experimental and clinical research · 2025Review
- Commonalities of platelet dysfunction in heart failure with preserved ejection fraction and underlying comorbidities.ESC heart failure · 2025Review
- Establishing and internally validating a predictive model for coronary heart disease incorporating triglyceride-glucose index, monocyte-to-high-density lipoprotein cholesterol ratio and conventional risk factors in patients experiencing chest pain and referred for invasive coronary angiography.Lipids in health and disease · 2025Article
- Joint association of triglyceride glucose index (TyG) and a body shape index (ABSI) with stroke incidence: a nationwide prospective cohort study.Cardiovascular diabetology · 2025Article
- The relationship between remote diffusion-weighted imaging lesions and the triglyceride-glucose index and clinical outcomes in patients with intracerebral hemorrhage.Frontiers in neurology · 2025Article
- Effect of Insulin Resistance on Prognosis of Intravenous Thrombolysis in Acute Ischemic Stroke Patients with or Without Type 2 Diabetes Mellitus.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- The association of the triglyceride-glucose index and its changes with 5-year all-cause mortality in patients with depression.Frontiers in psychiatry · 2025Article
- Changes in the metabolic score for insulin resistance index for risk prediction of stroke in middle-aged and older Chinese population.The EPMA journal · 2024Article
- Evaluation of Triglyceride Glucose Index in Patients with Patent Foramen Ovale Who Experienced Cryptogenic Stroke.Journal of clinical medicine · 2024Article
- Article
- Plasma growth factors maintain constitutive translation in platelets to regulate reactivity and thrombotic potential.Blood advances · 2024Article
- Association between Relative Thrombocytosis and Microalbuminuria in Adults with Mild Fasting Hyperglycemia.Journal of personalized medicine · 2024Article
- Triglyceride-glucose index prediction of stroke incidence risk in low-income Chinese population: a 10-year prospective cohort study.Frontiers in endocrinology · 2024Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
aimsPatients with conditions that are associated with insulin resistance such as obesity, type 2 diabetes mellitus, and polycystic ovary syndrome have an increased risk of thrombosis and a concurrent hyperactive platelet phenotype. Our aim was to determine whether insulin resistance of megakaryocytes/platelets promotes platelet hyperactivation. METHODS AND
resultsWe generated a conditional mouse model where the insulin receptor (IR) was specifically knocked out in megakaryocytes/platelets and performed ex vivo platelet activation studies in wild-type (WT) and IR-deficient platelets by measuring aggregation, integrin αIIbβ3 activation, and dense and α-granule secretion. Deletion of IR resulted in an increase in platelet count and volume, and blocked the action of insulin on platelet signalling and function. Platelet aggregation, granule secretion, and integrin αIIbβ3 activation in response to the glycoprotein VI (GPVI) agonist collagen-related peptide (CRP) were significantly reduced in platelets lacking IR. This was accompanied by a reduction in the phosphorylation of effectors downstream of GPVI. Interestingly, loss of IR also resulted in a reduction in insulin-like growth factor-1 (IGF-1)- and insulin-like growth factor-2 (IGF-2)-mediated phosphorylation of IRS-1, Akt, and GSK3β and priming of CRP-mediated platelet activation. Pharmacological inhibition of IR and the IGF-1 receptor in WT platelets recapitulated the platelet phenotype of IR-deficient platelets.
conclusionsDeletion of IR (i) increases platelet count and volume, (ii) does not cause platelet hyperactivity, and (iii) reduces GPVI-mediated platelet function and platelet priming by IGF-1 and IGF-2.
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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.