Affiliated Hospital of Shaoxing University of Endocrine and Metabolism Department, Zhejiang, China.
Sci Rep. 2022 Jan 7;12(1):188. doi: 10.1038/s41598-021-03912-6.
Patients with diabetes are more likely to be infected with Coronavirus disease 2019 (COVID-19), and the risk of death is significantly higher than ordinary patients. Dipeptidyl peptidase-4 (DPP4) is one of the functional receptor of human coronavirus. Exploring the relationship between diabetes mellitus targets and DPP4 is particularly important for the management of patients with diabetes and COVID-19. We intend to study the protein interaction through the protein interaction network in order to find a new clue for the management of patients with diabetes with COVID-19. Diabetes mellitus targets were obtained from GeneCards database. Targets with a relevance score exceeding 20 were included, and DPP4 protein was added manually. The initial protein interaction network was obtained through String. The targets directly related to DPP4 were selected as the final analysis targets. Importing them into String again to obtain the protein interaction network. Module identification, gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were carried out respectively. The impact of DPP4 on the whole network was analyzed by scoring the module where it located. 43 DPP4-related proteins were finally selected from the diabetes mellitus targets and three functional modules were found by the cluster analysis. Module 1 was involved in insulin secretion and glucagon signaling pathway, module 2 and module 3 were involved in signaling receptor binding. The scoring results showed that LEP and apoB in module 1 were the highest, and the scores of INS, IL6 and ALB of cross module associated proteins of module 1 were the highest. DPP4 is widely associated with key proteins in diabetes mellitus. COVID-19 may affect DPP4 in patients with diabetes mellitus, leading to high mortality of diabetes mellitus combined with COVID-19. DPP4 inhibitors and IL-6 antagonists can be considered to reduce the effect of COVID-19 infection on patients with diabetes.
糖尿病患者更易感染 2019 年冠状病毒病（COVID-19），且死亡风险显著高于普通患者。二肽基肽酶-4（DPP4）是人类冠状病毒的功能受体之一。探索糖尿病靶点与 DPP4 之间的关系，对于 COVID-19 合并糖尿病患者的管理尤为重要。我们拟通过蛋白质相互作用网络研究蛋白质相互作用，以期为 COVID-19 合并糖尿病患者的管理寻找新的线索。糖尿病靶点来源于 GeneCards 数据库，纳入相关评分大于 20 的靶点，手动添加 DPP4 蛋白。通过 String 获得初始蛋白质相互作用网络，选取与 DPP4 直接相关的靶点作为最终分析靶点，再次导入 String 获得蛋白质相互作用网络，分别进行模块识别、基因本体（GO）分析和京都基因与基因组百科全书（KEGG）通路分析，通过对其所在模块进行评分分析 DPP4 对整个网络的影响。最终从糖尿病靶点中筛选出 43 个与 DPP4 相关的蛋白，通过聚类分析发现 3 个功能模块。模块 1 涉及胰岛素分泌和胰高血糖素信号通路，模块 2 和模块 3 涉及信号受体结合。评分结果显示，模块 1 中 LEP 和 apoB 评分最高，模块 1 跨模块相关蛋白中 INS、IL6 和 ALB 评分最高。DPP4 与糖尿病的关键蛋白广泛相关。COVID-19 可能会影响糖尿病患者的 DPP4，导致糖尿病合并 COVID-19 患者死亡率升高。DPP4 抑制剂和 IL-6 拮抗剂可考虑用于降低 COVID-19 感染对糖尿病患者的影响。
