ArticleDiabetes2013
Nitric oxide directly promotes vascular endothelial insulin transport.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 114 citations in OpenAlex.
- Therapeutic Modulation of Nitric Oxide Pathways to Address Insulin Resistance in Cardiovascular-Kidney-Metabolic Syndrome.International journal of molecular sciences · 2026Review
- Higher salivary nitrite is associated with improved glycemic control and insulin sensitivity in patients with type 2 diabetes.Nutrition & metabolism · 2026Article
- From oversight to insight: the curious case of the endothelial insulin receptor.Blood vessels, thrombosis & hemostasis · 2026Review
- Beyond HbAFrontiers in endocrinology · 2026Review
- Emerging Roles of Post-Translational Modifications in Metabolic Homeostasis and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- The machinery of healthy vasodilatation: an overview.Pflugers Archiv : European journal of physiology · 2025Review
- Novel Function for Endothelial Protease-Activated Receptors in Modulating Insulin Receptor Activity With Implications for Diabetes.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise.Circulation research · 2025Review
- Atherosclerosis and Insulin Resistance: Is There a Link Between Them?Biomedicines · 2025Review
- Diabetes and its Silent Partner: A Critical Review of Hyperinsulinemia and its Complications.Current diabetes reviews · 2025Review
- Endothelial-Specific Reduction in Arf6 Impairs Insulin-Stimulated Vasodilation and Skeletal Muscle Blood Flow Resulting in Systemic Insulin Resistance in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Insulin resistance/hyperinsulinemia: an important cardiovascular risk factor that has long been underestimated.Frontiers in cardiovascular medicine · 2024Article
- Systemic nitric oxide metabolites and the chance of pre-diabetes regression to normoglycemia: A 9-year cohort study.BioImpacts : BI · 2024Article
- Roles of mitochondrial dynamics and mitophagy in diabetic myocardial microvascular injury.Cell stress & chaperones · 2023Review
- Circular RNA RSU1 promotes retinal vascular dysfunction by regulating miR-345-3p/TAZ.Communications biology · 2023Article
- Cysteine residues in signal transduction and its relevance in pancreatic beta cells.Frontiers in endocrinology · 2023Review
- Metformin's Impact on the Microvascular Response to Insulin.Endocrinology · 2022Review
- Age-Related Hearing Loss: The Link between Inflammaging, Immunosenescence, and Gut Dysbiosis.International journal of molecular sciences · 2022Review
- Effect of low-dose tadalafil once daily on glycemic control in patients with type 2 diabetes and erectile dysfunction: a randomized, double-blind, placebo-controlled pilot study.Diabetology & metabolic syndrome · 2022Article
- A New Approach to Overcome Insulin Resistance in Patients with Impaired Glucose Tolerance: The Results of a Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial of Efficacy and Safety of Subetta.Journal of clinical medicine · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Insulin resistance strongly associates with decreased nitric oxide (NO) bioavailability and endothelial dysfunction. In the vasculature, NO mediates multiple processes that affect insulin delivery, including dilating both resistance and terminal arterioles in skeletal muscle in vivo. However, whether NO directly regulates vascular endothelial cell (EC) insulin uptake and its transendothelial transport (TET) is unknown. We report in this article that L-N(G)-nitro-L-arginine methyl ester (L-NAME) pretreatment blocked, whereas L-arginine and sodium nitroprusside (SNP) each enhanced, EC uptake of fluorescein isothiocyanate (FITC)-labeled insulin. SNP also partly or fully reversed the inhibition of EC insulin uptake caused by L-NAME, wortmannin, the Src inhibitor PP1, and tumor necrosis factor-α. In addition, SNP promoted [(125)I]Tyr(A14)insulin TET by ~40%. Treatment with insulin with and without SNP did not affect EC cyclic guanosine monophosphate (cGMP) levels, and the cGMP analog 8-bromo-cGMP did not affect FITC-insulin uptake. In contrast, treatment with insulin and SNP significantly increased EC protein S-nitrosylation, the colocalization of S-nitrosothiol (S-NO) and protein-tyrosine phosphatase 1B (PTP1B), and Akt phosphorylation at Ser(473) and inhibited PTP1B activity. Moreover, a high-fat diet significantly inhibited EC insulin-stimulated Akt phosphorylation and FITC-insulin uptake that was partially reversed by SNP in rats. Finally, inhibition of S-nitrosylation by knockdown of thioredoxin-interacting protein completely eliminated SNP-enhanced FITC-insulin uptake. We conclude that NO directly promotes EC insulin transport by enhancing protein S-nitrosylation. NO also inhibits PTP1B activity, thereby enhancing insulin signaling.
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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.