ArticleNeuroscience2011
Phosphodiesterase-5 is a therapeutic target for peripheral neuropathy in diabetic mice.
Article in Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 96 citations in OpenAlex.
- LARP7 enhances the potential of dental pulp stem cells to promote peripheral nerve repair.Stem cells (Dayton, Ohio) · 2026Article
- Nervonic acid confers neuroprotection in a zebrafish model of diabetic neuropathy by promoting myelin repair and metabolic modulation.Frontiers in pharmacology · 2026Article
- Sildenafil reduced neuroinflammation and improved white matter injury in a rat model of term neonatal hypoxic-ischemic encephalopathy.Scientific reports · 2025Article
- Article
- Review
- Engineered miR-214 enriched Schwann cell-derived extracellular vesicles amplify therapeutic efficacy for peripheral neuropathy in T2D mice.Frontiers in cellular neuroscience · 2025Article
- RNA Interference Unleashed: Current Perspective of Small Interfering RNA (siRNA) Therapeutics in the Treatment of Neuropathic Pain.ACS pharmacology & translational science · 2024Review
- Polygonatum sibiricum (Huang Jing) polysaccharide reduces diabetic cardiomyopathy through increasing cyclic guanosine monophosphate-protein kinase G signaling in diabetic mice.Journal of diabetes investigation · 2024Article
- Evaluating the Antihyperalgesic Potential of Sildenafil-Metformin Combination and Its Impact on Biochemical Markers in Alloxan-Induced Diabetic Neuropathy in Rats.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Schwann cell-derived exosomes ameliorate peripheral neuropathy induced by ablation of dicer in Schwann cells.Frontiers in cellular neuroscience · 2024Article
- Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2023Review
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- The Influence of Sildenafil-Metformin Combination on Hyperalgesia and Biochemical Markers in Diabetic Neuropathy in Mice.Medicina (Kaunas, Lithuania) · 2023Article
- The efficacy of PDE5 inhibitors in diabetic patients.Andrology · 2023Review
- Neuritin Promotes Bone Marrow-Derived Mesenchymal Stem Cell Migration to Treat Diabetic Peripheral Neuropathy.Molecular neurobiology · 2022Article
- Nutraceutical Prevention of Diabetic Complications-Focus on Dicarbonyl and Oxidative Stress.Current issues in molecular biology · 2022Review
- Traumatic and Diabetic Schwann Cell Demyelination Is Triggered by a Transient Mitochondrial Calcium Release through Voltage Dependent Anion Channel 1.Biomedicines · 2022Article
- Sildenafil, a Type-5 Phosphodiesterase Inhibitor, Fails to Reverse Myeloid-Derived Suppressor Cell-Mediated T Cell Suppression in Cells Isolated From Tuberculosis Patients.Frontiers in immunology · 2022Article
- Sildenafil improves hippocampal brain injuries and restores neuronal development after neonatal hypoxia-ischemia in male rat pups.Scientific reports · 2021Article
- Pharmic Activation of PKG2 Alleviates Diabetes-Induced Osteoblast Dysfunction by Suppressing PLCOxidative medicine and cellular longevity · 2021Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Peripheral neuropathy is a common and major complication of diabetes, the underlying mechanisms of which are not fully understood. Using a mouse model of type II diabetes, the present study investigated the role of phosphodiesterase-5 (PDE5) in peripheral neuropathy. BKS.Cg-m+/+Leprdb/J (db/db) mice were treated with sildenafil, a specific inhibitor of PDE5, at doses of 2 and 10 mg/kg or saline. Levels of PDE5 and morphometric parameters in sciatic nerve tissue as well as the motor and sensory function were measured in these mice. In diabetic mice, PDE5 expression in sciatic nerve tissue was significantly upregulated, whereas the myelin sheath thickness, myelin basic protein (MBP), and subcutaneous nerve fibers were significantly reduced. Treatment with sildenafil significantly improved neurological function, assayed by motor and sensory conducting velocities and thermal and mechanical noxious stimuli, concomitantly with increases in myelin sheath thickness, MBP levels, and subcutaneous nerve fibers. In vitro, hyperglycemia upregulated PDE5 in Schwann cells and reduced Schwann cell proliferation, migration, and expression of brain-derived neurotrophic factor (BDNF). Blockage of PDE5 with sildenafil increased cyclic guanosine monophosphate (cGMP) and completely abolished the effect of hyperglycemia on Schwann cells. Sildenafil upregulated cGMP-dependent protein kinase G I (PKGI), whereas inhibition of PKGI with a PKG inhibitor, KT5823, suppressed the inhibitory effect of sildenafil on Schwann cells. These data indicate that hyperglycemia substantially upregulates PDE5 expression and that the cGMP/PKG signaling pathway activated by sildenafil mediates the beneficial effects of sildenafil on diabetic peripheral neuropathy.
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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.