Figure 1. A schematic diagram illustrating a hypothetical model of the impact of diabetes mellitus (DM)-caused metabolic disorder and insulin abnormality on male sexual and reproductive dysfunction. This schematic diagram shows that glucose metabolism disorder and IR in DM cause angioneuropathy through decreases in synthesis and release of NO and VEGF and increases in ET and AGEs in the endothelium leading to ED and retrograde ejaculation. On the other hand, abnormal glucose metabolism can lead to oxidative stress and the loss of zinc. Oxidative stress is a common mechanism underlying diabetic complications, and it also promotes changes in the above processes. Zinc is a strong antioxidant, and zinc deficiency aggravates oxidative stress injury. In addition, insulin deficiency in diabetic patients also causes HPGA damage, thereby reducing secretion of GnRH, FSH, LH, and T and leading to testicular atrophy, stromal cell (Sertoli and Leydig) atrophy, ST damage, and spermatogenic cell damage. All of these factors may act cooperatively to suppress sexual and reproductive function in men. Such a mechanism may serve to integrate the roles of these factors in the reduction of sperm density and motility and increase of deformity rate and sperm DNA fragmentation index, which may underlie the mechanisms through which DM caused male fertility and reproductive dysfunction. See the text for details. IR: Insulin resistance; NO: nitric oxide; VEGF: vascular endothelial growth factor; ET: endothelin; AGE: advanced glycation end product; ED: erectile dysfunction; HPGA: hypothalamic-pituitary-gonadal axis; GnRH: gonadotropin-releasing hormone; FSH: follicle stimulating hormone; LH: luteinizing hormone; T: testosterone; ST: seminiferous tubule; DFI: sperm DNA fragmentation index.