ArticleArteriosclerosis, thrombosis, and vascular biology2012
NOX4 pathway as a source of selective insulin resistance and responsiveness.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 67 citations in OpenAlex.
- Dissociation between liver fat content and fasting metabolic markers of selective hepatic insulin resistance in humans.European journal of endocrinology · 2024Article
- Interplay between energy metabolism and NADPH oxidase-mediated pathophysiology in cardiovascular diseases.Frontiers in pharmacology · 2024Review
- Transcriptome Analysis Reveals the Molecular Basis of Overfeeding-Induced Diabetes in Zebrafish.International journal of molecular sciences · 2023Article
- Molecular programming modulates hepatic lipid metabolism and adult metabolic risk in the offspring of obese mothers in a sex-specific manner.Communications biology · 2022Article
- NADPH Oxidases Connecting Fatty Liver Disease, Insulin Resistance and Type 2 Diabetes: Current Knowledge and Therapeutic Outlook.Antioxidants (Basel, Switzerland) · 2022Review
- Effect of Selenium Treatment on Central Insulin Sensitivity: A Proteomic Analysis in β-Amyloid Precursor Protein/Presenilin-1 Transgenic Mice.Frontiers in molecular neuroscience · 2022Article
- Astragaloside IV Improves the Barrier Damage in Diabetic Glomerular Endothelial Cells Stimulated by High Glucose and High Insulin.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- A nexus of miR-1271, PAX4 and ALK/RYK influences the cytoskeletal architectures in Alzheimer's Disease and Type 2 Diabetes.The Biochemical journal · 2021Article
- Hypoxia-inducible factor-1 mediates pancreatic β-cell dysfunction by intermittent hypoxia.American journal of physiology. Cell physiology · 2020Article
- Non-Coding RNAs as Potential Novel Biomarkers for Early Diagnosis of Hepatic Insulin Resistance.International journal of molecular sciences · 2020Review
- Swimming Exercise Protects against Insulin Resistance via Regulating Oxidative Stress through Nox4 and AKT Signaling in High-Fat Diet-Fed Mice.Journal of diabetes research · 2020Article
- Insulin Sensitivity Is Associated with Lipoprotein Lipase (International journal of molecular sciences · 2019Article
- Mechanisms of Insulin Action and Insulin Resistance.Physiological reviews · 2018Review
- ROS signaling and ER stress in cardiovascular disease.Molecular aspects of medicine · 2018Review
- Insulin therapy for type 2 diabetes - are we there yet? The d-Nav® story.Clinical diabetes and endocrinology · 2018Article
- Novel Insights into How Overnutrition Disrupts the Hypothalamic Actions of Leptin.Frontiers in endocrinology · 2018Review
- Hepatocyte ABCA1 Deletion Impairs Liver Insulin Signaling and Lipogenesis.Cell reports · 2017Article
- Deficient angiogenesis in redox-dead Cys17Ser PKARIα knock-in mice.Nature communications · 2015Article
- The role of mouse Akt2 in insulin-dependent suppression of adipocyte lipolysis in vivo.Diabetologia · 2015Article
- Neuregulin 1 Improves Glucose Tolerance in db/db Mice.PloS one · 2015Article
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2 authors at 1 institution in 1 country.
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Abstract
objectiveType 2 diabetes mellitus and related syndromes exhibit a deadly triad of dyslipoproteinemia, which leads to atherosclerosis; hyperglycemia, which causes microvascular disease; and hypertension. These features share a common, but unexplained, origin-namely, pathway-selective insulin resistance and responsiveness. Here, we undertook a comprehensive characterization of pathway-selective insulin resistance and responsiveness in liver and hepatocytes by examining 18 downstream targets of the insulin receptor, surveying the AKT, ERK, and NAD(P)H oxidase 4 pathways. METHODS AND
resultsInjection of insulin into hyperphagic, obese type 2 diabetic db/db mice failed to inactivate hepatic protein tyrosine phosphatase gene family members, a crucial action of NAD(P)H oxidase 4 previously thought to be required for all signaling through AKT and ERK. Insulin-stimulated type 2 diabetic livers unexpectedly produced an unusual form of AKT that was phosphorylated at Thr308 (pT308), with only weak insulin-stimulated phosphorylation at Ser473. Remarkably, knockdown or inhibition of NAD(P)H oxidase 4 in cultured hepatocytes recapitulated the entire complicated pattern of pathway-selective insulin resistance and responsiveness seen in vivo-namely, monophosphorylated pT308-AKT, impaired insulin-stimulated pathways for lowering plasma lipids and glucose, but continued lipogenic pathways and robust ERK activation.
conclusionsFunctional disturbance of a single molecule, NAD(P)H oxidase 4, is sufficient to induce the key harmful features of deranged insulin signaling in type 2 diabetes mellitus, obesity, and other conditions associated with hyperinsulinemia and pathway-selective insulin resistance and responsiveness.
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