Endocrine Abstracts

Background: Glucose-dependent insulinotropic polypeptide (GIP) secreted by K-cells in the intestine is an incretin that stimulates insulin secretion from pancreatic beta-cells. The aim of this study is to explore the extra-pancreatic effects of GIP on male fertility using diet-induced obese mice.

Methods: Male Swiss TO-mice (n = 8) on high-fat diet (HFD) or normal diet (ND) for 8-weeks received twice-daily intraperitoneal injections of (DAla²)GIP, mGIP(3-30) (25 nmol/kg bw) or saline vehicle (0.9% (w/v) NaCl) for 7 days. Metabolic parameters were regularly monitored. Terminal plasma and tissues were collected for hormone measurement. Male GIPR-Cre×Rosa26-GCaMP3 mice were used to provide evidence for GIP receptor in the testes.

Results: GIP receptor expression was found in the testis of GIPR-Cre×Rosa26-GCaMP3 mice. HFD mice exhibited significantly (P < 0.05-P < 0.001) higher body weight, blood glucose and energy intake compared to ND mice. mGIP(3-30) significantly (P < 0.05) decreased terminal blood glucose. Plasma GIP significantly increased after (DAla²)GIP while both (DAla²)GIP and mGIP(3-30) increased (P < 0.05-P < 0.01) corticosterone levels. (DAla²)GIP was able to increase (P < .0.05) testosterone levels compared to HFD. Sperm analysis showed a significant (P < 0.001) decrease in sperm count after HFD and remained unaltered by GIP. (DAla²)GIP and mGIP(3-30) decreased (P < 0.05-P < 0.01) motility compared to ND mice, displaying increased number of static sperm cells. However, progressive motility increased significantly (P < 0.05-P < 0.01) with (DAla²)GIP and mGIP(3-30) compared to ND and HFD mice. While HFD and GIP treatments did not alter testis weight, (DAla²)GIP and mGIP(3-30) significantly (P < 0.05-P < 0.01) increased tubule diameter in the testes. mGIP(3-30) significantly (P < 0.01-P < 0.001) decreased spermatogenic epithelium thickness compared to ND and HFD groups

Conclusion: These data suggest an active role for GIP in regulating fertility and reproductive physiology in males. Hence, targeting GIP receptors could be a unique therapeutic target for obese and diabetic male individuals.