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

Frontiers in Pharmacology

Pharmacology

Asmaa Monir Eltaweel¹  Jinlian Hua²  Maha K. Desouky³  Ahmed Hamed Arisha⁴  Ioan Banatean-Dunea⁵  Liana Mihaela Fericean⁵  Mona M. Ahmed⁶  Tarek Khamis⁷  Adel Abdelkhalek⁸  Amira Ebrahim Alsemeh⁹  Hanim M. Abdel-nour^1,10  Doaa M. Hendawy^1,10  Maha Abdelhamid Fathy^1,11  Marwa A. Habib^1,11 

[1] Basic Medical Science Department of Anatomy and Embryology, College of Medicine-King Saud Abdulaziz, University for Health Sciences—Kingdom of Saudi Arabia, Jeddah, Saudi Arabia;Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt;College of Veterinary Medicine/Shaanxi Centre of Stem Cells Engineering and Technology, Northwest Agriculture and Forestry University, Yangling, Shaanxi, China;Department of Anatomy, Faculty of Medicine, Minia University, Minia, Egypt;Department of Animal Physiology and Biochemistry, Faculty of Veterinary Medicine, Badr University in Cairo, Badr, Egypt;Department of Physiology and Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt;Department of Biology, Faculty of Agriculture, University of Life Sciences, King Mihai I” from Timisoara [ULST], Timisoara, Romania;Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt;Department of Pharmacology and Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt;Faculty of Veterinary Medicine, Badr University in Cairo, Badr, Egypt;Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt;Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt;Medical Physiology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt;

关键词: liraglutide;    GLP-1;    kisspeptin;    HPG axis;    antioxidant enzymes;    steroidogenesis;    TGF-β 1;   

DOI  :  10.3389/fphar.2023.1224985

 received in 2023-05-18, accepted in 2023-06-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: Glucagon-like peptide -1 (GLP-1) is released by intestinal cells to stimulate glucose-dependent insulin release from the pancreas. GLP-1 has been linked to ameliorating obesity and/or diabetic complications as well as controlling reproductive function. Liraglutide is a GLP-1 receptor agonist (GLP-1RA) with 97% homology with GLP-1. The main objective of this study was to investigate the ameliorative role of liraglutide in diabetic-induced reproductive dysfunction in male rats.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.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.

【 授权许可】

Unknown   
Copyright © 2023 Fathy, Alsemeh, Habib, Abdel-nour, Hendawy, Eltaweel, Abdelkhalek, Ahmed, Desouky, Hua, Fericean, Banatean-Dunea, Arisha and Khamis.