The protective effects and underlying mechanisms of dapagliflozin on diabetes-induced testicular dysfunction
作者机构：Department of UrologyPeking University Third HospitalBeijing 100191China Department of Endocrinology and MetabolismPeking University Third HospitalBeijing 100191China Department of Reproductive Medicine CenterPeking University Third HospitalBeijing 100191China
出 版 物：《Asian Journal of Andrology》 (亚洲男性学杂志（英文版）)
年 卷 期：2023年第25卷第3期
页 面：331-338页
核心收录：
学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：This work was supported by the National Natural Science Foundation of China(81901535 and 82071698) the Natural Science Foundation of Beijing Municipality(7222208) the National Key Research&Developmental Program of China(2021YFC2700203)
主 题：dapagliflozin diabetes glucagon-like peptide-1 receptor male infertility oxidative stress
摘 要：Male diabetic individuals present a marked impairment in fertility;however,knowledge regarding the pathogenic mechanisms and therapeutic strategies is *** new hypoglycemic drug dapagliflozin has shown certain benefits,such as decreasing the risk of cardiovascular and renal events in patients with *** so,until now,the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited ***,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 ***,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 *** 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 ***,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 ***(9-39)partially inhibited Akt *** results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase(PI3K)/Akt signaling *** results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.
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