ArticleArchives of pharmacal research2022
Empagliflozin mitigates type 2 diabetes-associated peripheral neuropathy: a glucose-independent effect through AMPK signaling.
Article in Archives of pharmacal research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Acetyllevocarnitine Hydrochloride for the Treatment of Diabetic Peripheral Neuropathy: A Phase 3 Randomized Clinical Trial in China.Diabetes · 2024Trial
- Toward Personalized NSAID Therapy in Osteoarthritis: The Right Patient, the Right Treatment, at the Right Time.Life (Basel, Switzerland) · 2026Review
- The Role of Sodium-Glucose Cotransporter 2 Inhibitors on Peripheral Nerves and Skeletal Muscle Function in Type 2 Diabetes.Journal of the ASEAN Federation of Endocrine Societies · 2026Review
- Neuroprotective Effects of Semaglutide in Cyclophosphamide-Induced Neuropathy: Restoring SIRT1/AMPK, PI3K/AKT/mTOR, and Antioxidant Pathways.Journal of molecular neuroscience : MN · 2026Article
- Innovative Diabetes Therapies and Impact on Peripheral and Autonomic Diabetic Neuropathies: A State-of-the-Art Review.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026Review
- Repurposed Systemic Pharmacologic Agents in Chronic Pain: Emerging Mechanistic and Clinical Insights.Journal of clinical medicine · 2026Review
- Central Sensitization and Nociplastic Pain: Shared Mechanisms in Fibromyalgia, Osteoarthritis, and Inflammatory Arthritis.Journal of pain research · 2026Review
- Sodium-Glucose Cotransporter 2 Inhibitors: An Emerging Therapeutic Approach for Ischemic Stroke Management.CNS drugs · 2025Review
- Translating Basic Science to Clinical Applications: A Narrative Review of Repurposed Pharmacological Agents in Preclinical Models of Diabetic Neuropathy.Biomedicines · 2025Review
- Tang Bi formula alleviates diabetic sciatic neuropathy via AMPK/PGC-1α/MFN2 pathway activation.Scientific reports · 2025Article
- Autophagy in Schwann cells: A potential pharmacotherapeutic target in diabetic peripheral neuropathy.World journal of diabetes · 2025Review
- Chrysin mitigates cyclophosphamide-triggered cardiotoxicity in rats: Insights into cardioprotection via Treg expression modulation and iNOS downregulation.Toxicology reports · 2025Article
- Empagliflozin as treatment in glycogen storage disease type IB patients.Molecular genetics and metabolism reports · 2025Article
- Modafinil Ameliorated Fibromyalgia Syndrome in Rats by Modulating Mast Cells and Microglia Activation Through Dopamine/Substance P/MRGPRX/Histamine and PI3K/p-Akt/NF-κB Signaling Pathways.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Management of cardiovascular disease by cerium oxide nanoparticles via alleviating oxidative stress and adipokine abnormalities.Scientific reports · 2025Article
- Article
- Novel glucose-lowering agents that benefit diabetic foot: icing on the cake.Frontiers in endocrinology · 2025Review
- The Potential Impact of SGLT2-I in Diabetic Foot Prevention: Promising Pathophysiologic Implications, State of the Art, and Future Perspectives-A Narrative Review.Medicina (Kaunas, Lithuania) · 2024Review
- Expression of Autophagy Markers LC3B, LAMP2A, and GRP78 in the Human Kidney during Embryonic, Early Fetal, and Postnatal Development and Their Significance in Diabetic Kidney Disease.International journal of molecular sciences · 2024Article
- Anti-depressant effect of Naringenin-loaded hybridized nanoparticles in diabetic rats via PPARγ/NLRP3 pathway.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic peripheral neuropathy (DPN) represents a severe microvascular condition that dramatically affects diabetic patients despite adequate glycemic control, resulting in high morbidity. Thus, recently, anti-diabetic drugs that possess glucose-independent mechanisms attracted attention. This work aims to explore the potentiality of the selective sodium-glucose cotransporter-2 inhibitor, empagliflozin (EMPA), to ameliorate streptozotocin-induced DPN in rats with insight into its precise signaling mechanism. Rats were allocated into four groups, where control animals received vehicle daily for 2 weeks. In the remaining groups, DPN was elicited by single intraperitoneal injections of freshly prepared streptozotocin and nicotinamide (52.5 and 50 mg/kg, respectively). Then EMPA (3 mg/kg/p.o.) was given to two groups either alone or accompanied with the AMPK inhibitor dorsomorphin (0.2 mg/kg/i.p.). Despite the non-significant anti-hyperglycemic effect, EMPA improved sciatic nerve histopathological alterations, scoring, myelination, nerve fibers' count, and nerve conduction velocity. Moreover, EMPA alleviated responses to different nociceptive stimuli along with improved motor coordination. EMPA modulated ATP/AMP ratio, upregulated p-AMPK while reducing p-p38 MAPK expression, p-ERK1/2 and consequently p-NF-κB p65 as well as its downstream mediators (TNF-α and IL-1β), besides enhancing SOD activity and lowering MDA content. Moreover, EMPA downregulated mTOR and stimulated ULK1 as well as beclin-1. Likewise, EMPA reduced miR-21 that enhanced RECK, reducing MMP-2 and -9 contents. EMPA's beneficial effects were almost abolished by dorsomorphin administration. In conclusion, EMPA displayed a protective effect against DPN independently from its anti-hyperglycemic effect, probably via modulating the AMPK pathway to modulate oxidative and inflammatory burden, extracellular matrix remodeling, and autophagy.
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