ArticleDiabetologia2014
Counteracting neuronal nitric oxide synthase proteasomal degradation improves glucose transport in insulin-resistant skeletal muscle from Zucker fa/fa rats.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Higher salivary nitrite is associated with improved glycemic control and insulin sensitivity in patients with type 2 diabetes.Nutrition & metabolism · 2026Article
- PIN (Protein Inhibitor of Neuronal Nitric Oxide Synthase) Modulates Glucose Uptake Through NO-Dependent and Independent Mechanisms in Rat Muscle Cells.Antioxidants (Basel, Switzerland) · 2026Article
- Mechanisms of exercise intervention in type 2 diabetes: a bibliometric and visualization analysis based on CiteSpace.Frontiers in endocrinology · 2024Review
- In Vitro Tests for a Rapid Evaluation of Antidiabetic Potential of Plant Species Containing Caffeic Acid Derivatives: A Validation by Two Well-Known Antidiabetic Plants,Molecules (Basel, Switzerland) · 2021Article
- Exercise training augments neuronal nitric oxide synthase dimerization in the paraventricular nucleus of rats with chronic heart failure.Nitric oxide : biology and chemistry · 2019Article
- Dystrophin R16/17-syntrophin PDZ fusion protein restores sarcolemmal nNOSμ.Skeletal muscle · 2018Article
- Response: "Commentary: A Hypothesis for Examining Skeletal Muscle Biopsy-Derived Sarcolemmal nNOSµ as Surrogate for Enteric nNOSα Function". nNOS(skeletal muscle) may be Evidentiary for Enteric NO-Transmission Despite nNOSµ/α Differences.Frontiers in medicine · 2016Article
- A Hypothesis for Examining Skeletal Muscle Biopsy-Derived Sarcolemmal nNOSμ as Surrogate for Enteric nNOSα Function.Frontiers in medicine · 2015Article
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Authors and funding
9 authors.
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Abstract
aims/hypothesisInsulin-mediated glucose transport and utilisation are decreased in skeletal muscle from type 2 diabetic and glucose-intolerant individuals because of alterations in insulin receptor signalling, GLUT4 translocation to the plasma membrane and microvascular blood flow. Catalytic activity of the muscle-specific isoform of neuronal nitric oxide synthase (nNOS) also participates in the regulation of glucose transport and appears to be decreased in a relevant animal model of drastic insulin resistance, the obese Zucker fa/fa rat. Our objective was to determine the molecular mechanisms involved in this defect.
methodsIsolated rat muscles and primary cultures of myocytes were used for western blot analysis of protein expression, immunohistochemistry, glucose uptake measurements and GLUT4 translocation assays.
resultsnNOS expression was reduced in skeletal muscle from fa/fa rats. This was caused by increased ubiquitination of the enzyme and subsequent degradation by the ubiquitin proteasome pathway. The degradation occurred through a greater interaction of nNOS with the chaperone heat-shock protein 70 and the co-chaperone, carboxyl terminus of Hsc70-interacting protein (CHIP). In addition, an alteration in nNOS sarcolemmal localisation was observed. We confirmed the implication of nNOS breakdown in defective insulin-induced glucose transport by demonstrating that blockade of proteasomal degradation or overexpression of nNOS improved basal and/or insulin-stimulated glucose uptake and GLUT4 translocation in primary cultures of insulin-resistant myocytes. CONCLUSIONS/
interpretationRecovery of nNOS in insulin-resistant muscles should be considered a potential new approach to address insulin resistance.
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