ArticleDiabetes2012
Hyperglycemia enhances IGF-I-stimulated Src activation via increasing Nox4-derived reactive oxygen species in a PKCζ-dependent manner in vascular smooth muscle cells.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
27 citing papers in PubMed, 61 citations in OpenAlex.
- The impact of high-sugar diets on central nervous system disorders: mechanisms, pathogenesis, and dietary implication.Annals of medicine · 2025Review
- The relationship of glycosylated hemoglobin A1c and Apolipoprotein A‑1 ratio on short-term prognosis in STEMI patients following PCI: a retrospective study.Scientific reports · 2025Article
- Insulin/IGF Axis and the Receptor for Advanced Glycation End Products: Role in Meta-inflammation and Potential in Cancer Therapy.Endocrine reviews · 2023Review
- Oxidative Regulation of Vascular CaAntioxidants (Basel, Switzerland) · 2022Review
- Redox Homeostasis in Thyroid Cancer: Implications in NaInternational journal of molecular sciences · 2022Review
- NADPH-Oxidase Derived Hydrogen Peroxide and Irs2b Facilitate Re-oxygenation-Induced Catch-Up Growth in Zebrafish Embryo.Frontiers in endocrinology · 2022Article
- Redox regulation of tyrosine kinase signalling: more than meets the eye.Journal of biochemistry · 2020Review
- The Role of NADPH Oxidases in the Etiology of Obesity and Metabolic Syndrome: Contribution of Individual Isoforms and Cell Biology.Antioxidants & redox signaling · 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
- Reactive Oxygen Species in Metabolic and Inflammatory Signaling.Circulation research · 2018Review
- Salidroside inhibits high-glucose induced proliferation of vascular smooth muscle cells via inhibiting mitochondrial fission and oxidative stress.Experimental and therapeutic medicine · 2017Article
- Down-regulation of Insulin Receptor Substrate 1 during Hyperglycemia Induces Vascular Smooth Muscle Cell Dedifferentiation.The Journal of biological chemistry · 2017Article
- Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders.Advances in pharmacology (San Diego, Calif.) · 2017Review
- Hyperglycemia stimulates p62/PKCζ interaction, which mediates NF-κB activation, increased Nox4 expression, and inflammatory cytokine activation in vascular smooth muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- ROS signaling and redox biology in endothelial cells.Cellular and molecular life sciences : CMLS · 2015Review
- Reactive Oxygen Species and Nuclear Factor Erythroid 2-Related Factor 2 Activation in Diabetic Nephropathy: A Hidden Target.Journal of diabetes & metabolism · 2015Article
- The coordinate cellular response to insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-2 (IGFBP-2) is regulated through vimentin binding to receptor tyrosine phosphatase β (RPTPβ).The Journal of biological chemistry · 2015Article
- YES, a Src family kinase, is a proximal glucose-specific activator of cell division cycle control protein 42 (Cdc42) in pancreatic islet β cells.The Journal of biological chemistry · 2014Article
- Article
- Regulation of NADPH oxidase 5 by protein kinase C isoforms.PloS one · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
IGF-I-stimulated sarcoma viral oncogene (Src) activation during hyperglycemia is required for propagating downstream signaling. The aim of the current study was to determine the mechanism by which hyperglycemia enhances IGF-I-stimulated Src activation and the role of NADPH oxidase 4 (Nox4) and protein kinase C ζ (PKCζ) in mediating this response in vascular smooth muscle cells (VSMCs). Nox4 expression was analyzed in VSMCs exposed to hyperglycemia. The role of Nox4-derived reactive oxygen species (ROS) in IGF-I-stimulated Src activation was investigated via knockdown of Nox4. Different isoforms of PKC were screened to investigate their role in hyperglycemia-induced Nox4. The oxidation of Src was shown to be a prerequisite for its activation in response to IGF-I during hyperglycemia. Hyperglycemia induced Nox4, but not Nox1, and p22 phagocyte oxidase (p22phox) expression and IGF-I stimulated Nox4/p22phox complex formation, leading to increased ROS generation. Knockdown of Nox4 prevented ROS generation and impaired the oxidation and activation of Src in response to IGF-I, whereas knockdown of Nox1 had no effect. PKCζ was shown to mediate the hyperglycemia-induced increase in Nox4 expression. The key observations in cultured VSMCs were confirmed in the diabetic mice. Nox4-derived ROS is responsible for the enhancing effect of hyperglycemia on IGF-I-stimulated Src activation, which in turn amplifies IGF-I-linked downstream signaling and biological actions.
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.