a Physiology Department, Minia University Faculty of Medicine, Minia 61111, Egypt.
b Histology and Cell Biology Department, Minia University Faculty of Medicine, Minia 61111, Egypt.
Appl Physiol Nutr Metab. 2018 Jun;43(6):617-624. doi: 10.1139/apnm-2017-0617. Epub 2018 Jan 19.
Diabetic nephropathy one of the major microvascular diabetic complications. Besides hyperglycemia, other factors contribute to the development of diabetic complications as the proinsulin connecting peptide, C-peptide. We described the role of C-peptide replacement therapy on experimentally induced diabetic nephropathy, and its potential mechanisms of action by studying the role of nitric oxide (NO) as a mediator of C-peptide effects by in vivo modulating its production by N-nitro-l-arginine methyl ester (L-NAME). Renal injury markers measured were serum urea, creatinine, tumor necrosis factor alpha, and angiotensin II, and malondialdehyde, total antioxidant, Bcl-2, and NO in renal tissue. In conclusion, diabetic induction resulted in islet degenerations and decreased insulin secretion with its metabolic consequences and subsequent renal complications. C-Peptide deficiencies in diabetes might have contributed to the metabolic and renal error, since C-peptide treatment to the diabetic rats completely corrected these errors. The beneficial effects of C-peptide are partially antagonized by L-NAME coadministration, indicating that NO partially mediates C-peptide effects.
糖尿病肾病是主要的糖尿病微血管并发症之一。除了高血糖，其他因素如胰岛素原连接肽 C 肽也会导致糖尿病并发症的发生。我们通过研究一氧化氮（NO）作为 C 肽作用的介导物的作用，以及通过体内调节其前体 N-硝基-L-精氨酸甲酯（L-NAME）的产生来描述 C 肽替代治疗对实验性诱导的糖尿病肾病的作用及其潜在的作用机制。测量的肾脏损伤标志物包括血清尿素、肌酐、肿瘤坏死因子-α和血管紧张素 II，以及肾组织中的丙二醛、总抗氧化剂、Bcl-2 和 NO。总之，糖尿病诱导导致胰岛退化和胰岛素分泌减少，及其代谢后果和随后的肾脏并发症。糖尿病中 C 肽的缺乏可能导致代谢和肾脏错误，因为 C 肽治疗糖尿病大鼠完全纠正了这些错误。C 肽的有益作用部分被 L-NAME 共同给药拮抗，表明 NO 部分介导 C 肽的作用。
