ArticleAsian journal of andrology
The protective effects and underlying mechanisms of dapagliflozin on diabetes-induced testicular dysfunction.
Article in Asian journal of andrology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Effects of empagliflozin on reproductive system in men without diabetes.Scientific reports · 2024Trial
- Beyond metabolic control: the potential role of antidiabetic therapies in modulating male reproductive function and spermatogenesis.Reviews in endocrine & metabolic disorders · 2026Review
- Oxidative Stress and Male Infertility: A Critical Analysis of Current Diagnostic and Therapeutic Methods.Antioxidants (Basel, Switzerland) · 2026Review
- Glucagon receptor blockade protects spermatogenesis by enhancing PFKFB3-mediated lactate production in Sertoli cells.Journal of translational medicine · 2026Article
- Antidiabetic agents and male fertility: unraveling the impact of glucose-lowering therapies on sperm quality in diabetic males-a narrative review.Translational andrology and urology · 2025Review
- GLP-1 receptor agonists show no detrimental effect on sperm quality in mouse models and cell lines.Endocrine · 2025Article
- Protective Effects of Chitosan-Loaded Pomegranate Peel Extract Nanoparticles on Infertility in Diabetic Male Rats.Current topics in medicinal chemistry · 2025Article
- Calcium Channels and Modulators as Potential Therapeutic Targets for Contraceptives and Male Fertility: A Scoping Review.Open access journal of contraception · 2025Review
- Management of male obesity-related secondary hypogonadism: A clinical update.World journal of experimental medicine · 2024Review
- Dapagliflozin ameliorates diabetes-induced spermatogenic dysfunction by modulating the adenosine metabolism along the gut microbiota-testis axis.Scientific reports · 2024Article
- Dapagliflozin Mitigated Elevated Disomic and Diploid Sperm in a Mouse Model of Diabetes and Recover the DisruptedBiomedicines · 2023Article
- Impacts of the DPP-4 Inhibitor Saxagliptin and SGLT-2 Inhibitor Dapagliflozin on the Gonads of Diabetic Mice.Biomedicines · 2023Article
- The gut metabolite 3-hydroxyphenylacetic acid rejuvenates spermatogenic dysfunction in aged mice through GPX4-mediated ferroptosis.Microbiome · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Male diabetic individuals present a marked impairment in fertility; however, knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory. The new hypoglycemic drug dapagliflozin has shown certain benefits, such as decreasing the risk of cardiovascular and renal events in patients with diabetes. Even so, until now, the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited clarification. Here, we found that dapagliflozin lowered blood glucose levels, alleviated seminiferous tubule destruction, and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice. Moreover, the glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin (9-39) had no effect on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice. We also found that dapagliflozin inhibited the testicular apoptotic process by upregulating the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL2) and X-linked inhibitor of apoptosis protein (XIAP) and inhibiting oxidative stress by enhancing the antioxidant status, including total antioxidant capacity, total superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity, as well as decreasing the level of 4-hydroxynonenal (4-HNE). Exendin (9-39) administration partially reversed these effects. Furthermore, dapagliflozin upregulated the glucagon-like peptide-1 (GLP-1) level in plasma and GLP-1R expression by promoting AKT8 virus oncogene cellular homolog (Akt) phosphorylation in testicular tissue. Exendin (9-39) partially inhibited Akt phosphorylation. These results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.
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