Abstract
Testicular structural and functional impairment is a serious complication in male diabetes mellitus (DM) patients that leads to impaired fertility in adulthood. In contrast to other endocrine therapies, islet transplantation (IT) can effectively prevent and even reverse diabetic nephropathy and myocardial damage. However, whether IT can alleviate diabetes-induced testicular injury remains unclear. In this study, we sought to investigate the effect of IT on diabetes-induced testicular damage. A diabetic rat model was established by streptozotocin injection. DM, IT, and insulin treatment (INS) groups were compared after 4 weeks of respective treatment. We confirmed that IT could effectively attenuate diabetes-induced testicular damage and recover sperm counts more extensively compared with INS in diabetic rats. In addition, significantly higher levels of superoxide dismutase (SOD) activity and lower contents of malondialdehyde (MDA) were detected in the testes of the IT group versus diabetic rats. Mechanism studies revealed that IT significantly activates the expression of Nrf-2, HO-1, and NQO-1 and inhibits upregulation of the NF-κB expression in response to DM, while INS only exhibit slight impact on the protein expression. Therefore, we speculate that IT may prevent the progression of testicular damage by downregulating oxidative stress and inhibiting inflammation via Nrf-2/HO-1 and NF-κB pathways.
Highlights
Diabetes mellitus (DM) is a chronic metabolic syndrome characterized by prolonged hyperglycemia [1] caused by either insulin secretion disorders, a lack of sensitivity of the cells to insulin, or both [2]
Blood glucose monitoring showed that the diabetic rats sustained hyperglycemia, while diabetic rats treated with insulin or islet transplantation (IT) showed a significant decrease in the blood glucose level
The blood glucose level of the IT group was consistently stable in the normal state, suggesting that IT performs better in lowering and stabilizing the blood glucose level compared with the insulin treatment (INS) group. (Figure 1(e))
Summary
Diabetes mellitus (DM) is a chronic metabolic syndrome characterized by prolonged hyperglycemia [1] caused by either insulin secretion disorders, a lack of sensitivity of the cells to insulin, or both [2]. The occurrence and development of testicular injury can seriously affect the quality of life of male diabetic patients [6]. The development of appropriate strategies to prevent loss of testicular germ cells and restore integrity of testicular tissue structures could present an indispensable approach to preserve or improve the fertility of young or adult men patients. Low amounts of free radicals are essential for spermatogenesis and sperm maturation, the testicles are highly susceptible to increases in these species compared with other tissues. Protein glycosylation and glucose autooxidation can cause lipid peroxidation (LPO), which further leads to formation of free radicals.
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