Abstract
Background:
Diabetes mellitus (DM) can negatively influences the hypothalamic–pituitary–gonadal axis (HPGA) and male fertility.

Aim:
To investigate the effects of Citrullus colocynthis (CC) extract on HPGA regulation and pancreatic glucose transporter 2 (GLUT2) expression in streptozotocin induced DM in male rats, together with sperm morphology, motility, and count.

Methods:
Thirty-two adult male rats were divided into 4 groups of 8 animals each as negative control, positive control, treatment 1 (250 mg/kg body weight), and treatment 2 (500 mg/kg) of CC extract, respectively. All groups were induced with DM, except group one. Treatments were given orally for 30 consecutive days. After animal scarification using deep anesthesia, blood samples were collected for hematological and biochemical analyses, and tissue samples were obtained for histopathological and immunohistochemical studies (pancreas) and semen analysis (testicles).

Results:
Treatment 2 significantly (p≤0.05) decreased blood glucose and glycated hemoglobin levels with marked elevation in serum insulin levels. The significant reduction of gonadotropin-releasing hormone in diabetic rats was substantially recovered by treatment 2, whereas no changes in luteinizing hormone, follicular stimulating hormone, and testosterone levels were recorded. Sperm motility was significantly increased in diabetic rats receiving treatment 1 of CC extract. Histopathological results have shown various alterations in the testis and pancreatic tissue in diabetic rats, which were improved almost to normal levels by different doses of CC extract. Immunohistochemical analysis showed complete restoration and normal localization of GLUT2 in pancreatic beta cells after treatment with CC extract.

Conclusion:
CC extract ameliorates diabetic complications through a potent natural effect against HPGA dysfunction, pancreatic and testicular alteration, and GLUT2 overexpression in pancreatic beta cells.

Key words: Diabetes mellitus; GLUT2; Hypothalamic-pituitary-gonadal axis; Plant extract; Semen analysis.