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

• Published in: Journal of cellular physiology 2019-06, Vol.234 (6), p.9351-9357
• Main Authors: Nazmy, Walaa Hassan, Elbassuoni, Eman Abdelmonem, Ali, Fatma Farrag, Rifaai, Rehab Ahmed
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Apoptosis - drug effects; Beta cells; C-Peptide - pharmacology; C-Peptide - therapeutic use; Combined treatment; C‐peptide; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Type 1 - drug therapy; Fertility; fertility impairments; Follicle-stimulating hormone; Histopathology; Infertility; Infertility, Male - drug therapy; Insulin; Insulin - pharmacology; Insulin - therapeutic use; Leukemia; Luteinizing hormone; Lymphoma; Male; Malondialdehyde; Oxidative Stress - drug effects; Parameter estimation; Peptides; Physiological effects; Rats; Rodents; Sexual behavior; Sperm; Sperm Count; Streptozocin; Testes; testicular dysfunction; Testis - drug effects; Testis - pathology; Testis - physiopathology; Testosterone
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.27618

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. Diabetes mellitus (DM) has a detrimental effect on rat testicular function and architecture including hypogonadism and decreased sperm count and motility. C‐peptide with or without insulin treatment efficiently reversed all negative effects of DM on rat testes, probably via its hypoglycemic, antioxidant, and antiapoptotic mechanisms with subsequent improvement in testicular function and architecture.