2. Academic Validation
  3. Exenatide improves hypogonadism and attenuates inflammation in diabetic mice by modulating gut microbiota

Exenatide improves hypogonadism and attenuates inflammation in diabetic mice by modulating gut microbiota

  • Int Immunopharmacol. 2023 May 19;120:110339. doi: 10.1016/j.intimp.2023.110339.
Yuping Chen 1,  Anmei Shu 1,  Ming Jiang 2,  Jinjin Jiang 3,  Qiu Du 4,  Tianbao Chen 5,  Chris Shaw 5,  Wengang Chai 2,  TianQi Chao 2,  Xiangzhe Li 2,  Qin Wu 6,  Cuixiang Gao 7
Affiliations

Affiliations

  • 1 Department of Basic Medical Science, Jiangsu Vocational College of Medicine, Yancheng 224005, Jiangsu, China.
  • 2 School of Pharmacy, Jiangsu Vocational College of Medicine, Yancheng 224005, Jiangsu, China.
  • 3 School of Medical Technology, Jiangsu Vocational College of Medicine, Yancheng 224005, Jiangsu, China.
  • 4 Department of pharmacy, Nanjing Hospital of Chinese Medicine, NanJing 210001, Jiangsu, China.
  • 5 School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
  • 6 School of Medicine, Jiangsu Vocational College of Medicine, Yancheng 224005, Jiangsu, China. Electronic address: [email protected].
  • 7 Department of Basic Medical Science, Jiangsu Vocational College of Medicine, Yancheng 224005, Jiangsu, China. Electronic address: [email protected].
PMID: 37210914 DOI: 10.1016/j.intimp.2023.110339
Abstract

With the rising incidence of diabetes and its onset at a younger age, the impact on the male reproductive system has gradually gained attention. Exenatide is a glucagon-like peptide-1 receptor agonist effective in the treatment of diabetes. However, its role in diabetes-induced reproductive complications has rarely been reported. The study aimed to investigate the mechanism by which exenatide improved diabetic hypogonadism by regulating gut microbiota (GM) mediated inflammation. C57BL/6J mice were equally divided into normal control (NC), diabetic model control (DM) and exenatide-treated (Exe) groups. Testicular, pancreatic, colonic, and fecal samples were collected to assess microbiota, morphologic damage, and inflammation. Exenatide significantly reduced the fasting blood glucose (FBG) level in diabetic mice, increased the testosterone level, ameliorated the pathological morphological damage of islet, colon, and testes, and reduced the expression of pro-inflammatory factors, tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 in colon and testis. Furthermore, exenatide significantly reduced the abundance of some pathogenic bacteria, such as Streptococcaceae and Erysipelotrichaceae, and increased that of beneficial bacteria Akkermansia. Probiotics, such as Lactobacillus were negatively correlated with TNF-α, nuclear factor-kappa-B (NF-κB), IL-6, and FBG. Conditional pathogenic bacteria such as Escherichia/Shigella Streptococcus were positively correlated with TNF-α, NF-κB, IL-6, and FBG. The fecal bacteria transplantation experiment revealed that the abundance of pathogenic bacteria, Peptostreptococcaceae, significantly decreased from Exe group mice to pseudo-sterile diabetic mice, and the pathological damage to testes was also alleviated. These data suggested the protective effects of exenatide on male reproductive damage induced by diabetes by regulating GM.

Keywords

Diabetes mellitus; Exenatide; Gut microbiota; Hypogonadism; Inflammation.

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