Dapagliflozin promising treatment for male fertility in diabetic patients: Study
China: Findings from a recent study published in the Asian Journal of Andrology suggest that dapagliflozin may be a promising treatment for male patients with both diabetes and impaired fertility.
The study showed that in diabetic mice treatment with dapagliflozin improved sperm quality, alleviated impaired spermatogenesis, and ameliorated apoptosis and the overall oxidative stress status in the testicular tissue. This may be mediated by the activation of the GLP-1R/PI3K/Akt signaling pathway.
Male diabetes patients present a marked impairment in fertility, however, there is no clarity on the knowledge regarding the pathogenic mechanisms and therapeutic strategies. Dapagliflozin, the new hypoglycemic drug, has shown certain benefits such as reducing the risk of cardiovascular and renal events in diabetes patients. However, the effects and underlying mechanisms of dapagliflozin on diabetic male infertility demand clarification.
Against the above background, Zhi-Chao Luo, Department of Urology, Peking University Third Hospital, Beijing, China, and colleagues aimed to investigate the influences of dapagliflozin on spermatogenesis and sperm quality in diabetic mice and also explored the underlying mechanisms.
Based on the study, the researchers reported the following findings:
- Dapagliflozin lowered blood glucose levels, alleviated seminiferous tubule destruction, and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice.
- There was no effect of the glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice.
- 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 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 findings suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway," the researchers conclude.
"Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction," they wrote.
