Proinsulin C-peptide as an alternative or combined treatment with insulin for management of testicular dysfunction and fertility impairments in streptozotocin-induced type 1 diabetic male rats

Diabetes mellitus (DM) is closely associated with male infertility and sexual dysfunction. Recent data indicate that the proinsulin C-peptide (CP) exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. So, this study was done to investigate the effect of C-peptide with or without insulin treatment on testicular function and architecture in diabetic rats. Rats were divided into the following groups: control, diabetic, and diabetic groups treated with either CP alone or combined with insulin. Tested parameters included, estimation of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and glucose levels, testicular samples for histopathology and estimation of malondialdehyde (MDA), total antioxidant capacity (TAC), and B-cell leukemia/lymphoma-2 (BCL-2) levels as well as sperm count and motility. Results showed that DM caused a severe alteration in hormonal profile and reduced sperm parameters along with increased MDA and decrease in both TAC and BCL-2 levels. CP alone or with insulin treatment efficiently reversed all the negative effects of DM on rat testes, with maximum improvement in the combined regimen. Proposed mechanisms may involve its hypoglycemic, antioxidant, and antiapoptotic properties. Thus, CP could substitute for or better combined with insulin to prevent or retard diabetic-induced testicular dysfunction.