Search

Purpose. This study aimed to investigate the potential mechanism underlying the therapeutic effect of sildenafil in combination with islet transplantation for diabetic peripheral neuropathy. Methods. A streptozotocin-induced diabetic mouse model was established to evaluate the effects of islet transplantation and sildenafil intervention. The mice were subjected to different interventions for 6 weeks, and histopathological staining and immunohistochemistry techniques were employed to examine the pathological changes and protein expressions of BDNF, MBP, and cleaved caspase-3 in the sciatic nerve tissue. Moreover, RSC96 cells were cocultured with islet cells and sildenafil under high glucose conditions to investigate the potential involvement of the mTOR/S6K1 pathway, BDNF, and MBP proteins. Western blotting was used to detect protein expression in each group. Results. The results showed that islet transplantation can restore sciatic nerve injury in diabetic mice, and sildenafil can enhance the therapeutic effect of islet transplantation. In addition, the combination of sildenafil and islet cells significantly upregulated the expression levels of mTOR/S6K1, BDNF, and MBP in RSC96 cells under high glucose conditions. Conclusions. Islet transplantation can reverse sciatic nerve injury in diabetic mice, and islet cells exhibit a protective effect on RSC96 cells under high glucose conditions via the activation of the mTOR/S6K1 pathway. Sildenafil enhances the therapeutic effect of islet transplantation, which may represent a potential treatment strategy for diabetic peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Background: Glycaemic control is one of the most effective strategies for the treatment of diabetes-related erectile dysfunction (DMED). Compared to conventional anti-diabetic drugs and insulin, islet transplantation is more effective in the treatment of diabetic complications. The aim of this study was to investigate the efficacy of islet transplantation for reversing advanced-stage DMED in rats and to observe its influence on corpus cavernosum fibrosis. Methods: Wistar rats were intraperitoneally injected with streptozotocin to establish a diabetes model. After 12 weeks, the rats were divided into 4 groups: diabetic, insulin, islet transplantation, and normal control. Following supplementation, the changes in blood glucose and weight were determined sequentially. Penile erectile function was evaluated by apomorphine experiments in the fourth week, and the penile corpus cavernosum was also collected for assessment by Masson staining, immunohistochemistry and Western blot to observe the spongy tissue and the related cellular changes at the molecular level. Results: Islet transplantation significantly ameliorated penile erectile function in advanced-stage diabetic rats. The ratio of corpus cavernosum smooth muscle cells to fibroblasts and the expression level of α-SMA in the islet transplantation group were significantly higher than those in the diabetic and insulin groups. In addition, the expression levels of TGF-β1, p-Samd2, and connective tissue growth factor (CTGF) in the islet transplantation and insulin groups were much lower than those in the diabetic group, while those in the islet transplantation group were significantly lower than those in the insulin group. Conclusions: Our findings strongly suggest that islet transplantation can promote the regeneration of smooth muscle cells and ameliorate corpus cavernosum fibrosis to restore its normal structure in advanced-stage diabetic rats. The possible mechanism of ameliorating corpus cavernosum fibrosis by islet transplantation may be associated with improvement of the hyperglycaemic status in diabetic rats, thereby inhibiting the TGF-β1/Samd2/CTGF pathway. [ABSTRACT FROM AUTHOR]