Chandra Phool, Sachan Neetu, Saraswat Nikita, Vyawahare Niraj
Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad-244001, (U.P), India.
Maharana Pratap College of Pharmacy, Kothi, Mandhana, Kanpur (UP)-209 217, India.
Curr Mol Pharmacol. 2024;17(1):e280323215026. doi: 10.2174/1874467217666230328084215.
Diabetic mellitus is responsible for triggering many conditions, such as neuropathy, nephropathy, and retinopathy. Hyperglycemia leads to the development of oxidative stress conditions, activation of pathways, and generation of metabolites, leading to complications like neuropathy and nephropathy.
This paper aims to discuss the mechanism of actions, pathways, and metabolites triggered due to the development of neuropathy and nephropathy post-long-haul diabetes in patients. The therapeutic targets are also highlighted, proving to be a potential cure for such conditions.
Research works were searched from international and national databases with keywords like "diabetes," "diabetic nephropathy," "NADPH," "oxidative stress," "PKC," "Molecular mechanisms," " cellular mechanisms," "complications of diabetes," and "factors." The databases searched were PubMed, Scopus, Directory of open access journals, Semantic Scholar, Core, Europe PMC, EMBASE, Nutrition, FSTA- Food Science and Technology, Merck Index, Google Scholar, PubMed, Science Open, MedlinePlus, Indian citation index, World Wide Science, and Shodhganga.
Pathways causing protein kinase C (PKC) activation, free radical injury, oxidative stress, and aggravating the conditions of neuropathy and nephropathy were discussed. In diabetic neuropathy and nephropathy, neurons and nephrons are affected to the extent that their normal physiology is disturbed, thus leading to further complications and conditions of loss of nerve sensation in diabetic neuropathy and kidney failure in diabetic nephropathy. Current treatment options available for the management of diabetic neuropathy are anticonvulsants, antidepressants, and topical medications, including capsaicin. According to AAN guidelines, pregabalin is recommended as the first line of therapy, whereas other drugs currently used for treatment are gabapentin, venlafaxine, opioids, amitriptyline, and valproate. Drug targets for treating diabetic neuropathy must suppress the activated polyol pathways, kinase C, hexosamine, and other pathways, which amplify neuroinflammation. Targeted therapy must focus on the reduction of oxidative stress and proinflammatory cytokines and suppression of neuroinflammation, NF-κB, AP-1, etc. Conclusion: Potential drug targets must be considered for new research on the treatment of neuropathy and nephropathy conditions.
糖尿病会引发多种病症，如神经病变、肾病和视网膜病变。高血糖会导致氧化应激状态的发展、信号通路的激活以及代谢产物的生成，进而引发神经病变和肾病等并发症。
本文旨在探讨长期糖尿病患者发生神经病变和肾病后所触发的作用机制、信号通路及代谢产物。还强调了治疗靶点，证明其可能是治疗此类病症的方法。
从国际和国内数据库中检索研究文献，关键词包括“糖尿病”“糖尿病肾病”“烟酰胺腺嘌呤二核苷酸磷酸（NADPH）”“氧化应激”“蛋白激酶C（PKC）”“分子机制”“细胞机制”“糖尿病并发症”和“因素”。检索的数据库有PubMed、Scopus、开放获取期刊目录、语义学者、Core、欧洲生物医学信息学研究所（Europe PMC）、医学数据库（EMBASE）、营养学、食品科学与技术文摘数据库（FSTA）、默克索引、谷歌学术、PubMed、科学开放、医学线上plus、印度引文索引、世界科学数据库和印度数字图书馆（Shodhganga）。
讨论了导致蛋白激酶C（PKC）激活、自由基损伤、氧化应激以及加重神经病变和肾病病情的信号通路。在糖尿病神经病变和肾病中，神经元和肾单位受到影响，其正常生理功能受到干扰，从而导致糖尿病神经病变中进一步的并发症和神经感觉丧失，以及糖尿病肾病中的肾衰竭。目前可用于治疗糖尿病神经病变的治疗方法有抗惊厥药、抗抑郁药和局部用药，包括辣椒素。根据美国神经病学学会（AAN）指南，普瑞巴林被推荐为一线治疗药物，而目前用于治疗糖尿病神经病变的其他药物有加巴喷丁、文拉法辛、阿片类药物、阿米替林和丙戊酸盐。治疗糖尿病神经病变的药物靶点必须抑制激活的多元醇通路、蛋白激酶C、己糖胺和其他放大神经炎症的信号通路。靶向治疗必须专注于降低氧化应激和促炎细胞因子，并抑制神经炎症、核因子κB（NF-κB）、激活蛋白-1（AP-1）等。结论：在治疗神经病变和肾病病症的新研究中，必须考虑潜在的药物靶点。
