Liraglutide ameliorates diabetic-induced testicular dysfunction in male rats: role of GLP-1/Kiss1/GnRH and TGF-β/Smad signaling pathways

利拉鲁肽改善雄性大鼠糖尿病引起的睾丸功能障碍:GLP-1/Kiss1/GnRH 和 TGF-β/Smad 信号通路的作用

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作者:Maha Abdelhamid Fathy, Amira Ebrahim Alsemeh, Marwa A Habib, Hanim M Abdel-Nour, Doaa M Hendawy, Asmaa Monir Eltaweel, Adel Abdelkhalek, Mona M Ahmed, Maha K Desouky, Jinlian Hua, Liana Mihaela Fericean, Ioan Banatean-Dunea, Ahmed Hamed Arisha, Tarek Khamis2

Conclusion

GLP-1RAs ameliorated the deleterious effects of diabetes on reproductive function by targeting GLP-1/leptin/kiss1/GnRH, steroidogenesis, and TGF- β/Smad pathways.

Methods

Rats were randomly allocated into 3 groups; a control group, a diabetic group, and a liraglutide-treated diabetic group.

Results

In the diabetic group, a significant increase in BMI, FBG, HbA1c, HOMA-IR, TC, TAG, LDL, IL6, TNFα, and MDA, as well as decreased serum insulin, HDL, GSH, total testosterone, LH, and FSH, were shown compared to the control group. Furthermore, A significant downregulation in relative hypothalamic gene expression of GLP-1R, PPAR-α, PGC-1α, kiss, kiss1R, leptin, leptin R, GnRH GLP-1R, testicular PGC-1α, PPARα, kiss1, kiss1R, STAR, CYP17A1, HSD17B3, CYP19A, CYP11A1, and Smad7, as well as upregulation in hypothalamic GnIH and testicular TGF- β and Smad2 expression, were noticed compared to the control group. Liraglutide treatment significantly improved such functional and structural reproductive disturbance in diabetic rats.

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