Saxagliptin alleviates erectile dysfunction through increasing stromal cell-derived factor-1 in diabetes mellitus

Area of Science:

• Endocrinology and Metabolism
• Urology and Andrology

Background:

• Diabetes mellitus-induced erectile dysfunction (DMED) is a common complication of diabetes with limited treatment options.
• Phosphodiesterase type 5 inhibitors are first-line treatments for ED but show poor efficacy in DMED.
• Saxagliptin (Sax), a dipeptidyl peptidase-4 inhibitor (DPP-4i), is used for type 2 diabetes and targets stromal cell-derived factor-1 (SDF-1), a factor potentially beneficial for DM complications.

Purpose of the Study:

• To investigate the therapeutic effects of Saxagliptin on DMED.
• To elucidate the underlying molecular mechanisms of Saxagliptin in managing DMED.

Main Methods:

• A rat model of DMED was established using streptozotocin.
• Experimental groups included control, DMED, and DMED treated with Saxagliptin.
• In vitro studies utilized high glucose-exposed corpus cavernosum smooth muscle cells (CCSMCs) treated with Saxagliptin and an SDF-1 receptor inhibitor (AMD3100).

Main Results:

• Saxagliptin partially improved erectile function in DMED rats.
• Treatment with Saxagliptin led to decreased DPP-4 expression, increased SDF-1 levels, enhanced PI3K/AKT pathway activity, and reduced endothelial dysfunction, oxidative stress, and apoptosis in penile tissues.
• Saxagliptin mitigated oxidative stress and apoptosis in high glucose-treated CCSMCs, effects partially reversed by AMD3100.

Conclusions:

• Saxagliptin alleviates DMED by upregulating SDF-1 and activating the PI3K/AKT pathway.
• The therapeutic benefits of Saxagliptin involve moderating endothelial dysfunction, oxidative stress, and apoptosis in the corpus cavernosum.
• These findings suggest that DPP-4 inhibition may be a promising therapeutic strategy for managing DMED.