ArticleThe Journal of biological chemistry2017
Down-regulation of Insulin Receptor Substrate 1 during Hyperglycemia Induces Vascular Smooth Muscle Cell Dedifferentiation.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Effect of Canagliflozin Pretreatment on the Efficacy of Insulin Therapy to Rescue Type 1 Diabetes-Related Bone Fragility in Male Mice.Calcified tissue international · 2026Article
- Maternal diabetes mellitus during pregnancy as a risk factor for strabismus and refractive errors in the offspring-A large-scale national study.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026Article
- The Role and Diagnostic Potential of Insulin-like Growth Factor 1 in Diabetic Retinopathy and Diabetic Macular Edema.International journal of molecular sciences · 2025Review
- Integrated multi-omic high-throughput strategies across-species identified potential key diagnostic, prognostic, and therapeutic targets for atherosclerosis under high glucose conditions.Molecular and cellular biochemistry · 2025Article
- Upregulation of miRNA-200c during Disease Progression in COVID-19 Patients.Journal of clinical medicine · 2022Article
- Metabolic Syndrome-Related Kidney Injury: A Review and Update.Frontiers in endocrinology · 2022Review
- Chronic and Intermittent Hyperglycemia Modulates Expression of Key Molecules of PI3K/AKT Pathway in Differentiating Human Visceral Adipocytes.International journal of molecular sciences · 2021Article
- Imatinib improves insulin resistance and inhibits injury-induced neointimal hyperplasia in high fat diet-fed mice.European journal of pharmacology · 2021Article
- Metformin Suppresses the Progress of Diabetes-Accelerated Atherosclerosis by Inhibition of Vascular Smooth Muscle Cell Migration Through AMPK-Pdlim5 Pathway.Frontiers in cardiovascular medicine · 2021Article
- Insulin‑receptor substrate 1 protects against injury in endothelial cell models of ox‑LDL‑induced atherosclerosis by inhibiting ER stress/oxidative stress‑mediated apoptosis and activating the Akt/FoxO1 signaling pathway.International journal of molecular medicine · 2020Article
- Serum microRNA-204 levels are associated with long-term cardiovascular disease risk based on the Framingham risk score in patients with type 2 diabetes: results from an observational study.Journal of geriatric cardiology : JGC · 2020Article
- IGF-1 and cardiovascular disease.Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society · 2019Review
- Hyperglycemia induces vascular smooth muscle cell dedifferentiation by suppressing insulin receptor substrate-1-mediated p53/KLF4 complex stabilization.The Journal of biological chemistry · 2019Article
- Inhibition of Aberrant IGF-I Signaling in Diabetic Male Rat Retina Prevents and Reverses Changes of Diabetic Retinopathy.Journal of diabetes research · 2019Article
- IRS-1 increases TAZ expression and promotes osteogenic differentiation in rat bone marrow mesenchymal stem cells.Biology open · 2018Article
- MicroRNA-dependent regulation of KLF4 by glucose in vascular smooth muscle.Journal of cellular physiology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Diabetes is a major risk factor for the development of atherosclerosis, but the mechanism by which hyperglycemia accelerates lesion development is not well defined. Insulin and insulin-like growth factor I (IGF-I) signal through the scaffold protein insulin receptor substrate 1 (IRS-1). In diabetes, IRS-1 is down-regulated, and cells become resistant to insulin. Under these conditions, the IGF-I receptor signals through an alternate scaffold protein, SHPS-1, resulting in pathophysiologic stimulation of vascular smooth muscle cell (VSMC) migration and proliferation. These studies were undertaken to determine whether IRS-1 is functioning constitutively to maintain VSMCs in their differentiated state and, thereby, inhibit aberrant signaling. Here we show that deletion of IRS-1 expression in VSMCs in non-diabetic mice results in dedifferentiation, SHPS-1 activation, and aberrant signaling and that these changes parallel those that occur in response to hyperglycemia. The mice showed enhanced sensitivity to IGF-I stimulation of VSMC proliferation and a hyperproliferative response to vascular injury. KLF4, a transcription factor that induces VSMC dedifferentiation, was up-regulated in IRS-1
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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.