Gao Nan, Chen Xiteng, Yang Jun, Jiang Yuanfeng, Bu Shaochong, Bai Xiaomei, Kou Zhenyu, Li Chunjun, Tian Fang
Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
Department of Endocrinology, Tianjin Union Medical Center, Nankai University, Tianjin, China.
Biochem Biophys Rep. 2025 Jun 24;43:102099. doi: 10.1016/j.bbrep.2025.102099. eCollection 2025 Sep.
Insulin therapy is still the most important treatment for T2DM, but the discussion about whether insulin brings more benefits or harms to T2DM patients has not stopped. Therefore, we used high-throughput RNA sequencing to investigate the role of insulin in T2DM and its molecular changes.
We collected peripheral blood samples from 16 patients with T2DM, and performed RNA-seq on peripheral blood mononuclear cells. Bioinformatics analysis and machine learning were uesd to identify the key differential genes and transcription factor networks. In addition, we performed the flow cytometry and staining to observe ROS level and endothelial-monocyte adhesion in PBMCs of both groups.
A total of 529 differential genes were identified by bioinformatics analysis. 8 genes were identified as key genes, among which IL-6 had high importance in the random forest model. In transcription factor analysis, IL-6, RETN, CTSG and ELANE have abundant transcriptional regulatory relationships. Flow cytometry showed that ROS production, phagocytosis, leukocyte adhesion in insulin treatment group were lower than that in non-insulin treatment group.
Insulin therapy is bidirectional, it can cause islet B cell damage and vascular complications, but also can reduce the level of inflammation and oxidative stress.
胰岛素治疗仍然是2型糖尿病最重要的治疗方法，但关于胰岛素对2型糖尿病患者是带来更多益处还是危害的讨论从未停止。因此，我们使用高通量RNA测序来研究胰岛素在2型糖尿病中的作用及其分子变化。
我们收集了16例2型糖尿病患者的外周血样本，并对外周血单个核细胞进行RNA测序。使用生物信息学分析和机器学习来识别关键差异基因和转录因子网络。此外，我们进行了流式细胞术和染色，以观察两组外周血单个核细胞中的活性氧水平和内皮细胞与单核细胞的黏附情况。
通过生物信息学分析共鉴定出529个差异基因。8个基因被确定为关键基因，其中白细胞介素-6在随机森林模型中具有高度重要性。在转录因子分析中，白细胞介素-6、网膜素、组织蛋白酶G和弹性蛋白酶原具有丰富的转录调控关系。流式细胞术显示，胰岛素治疗组的活性氧生成、吞噬作用、白细胞黏附低于非胰岛素治疗组。
胰岛素治疗具有双向性，它可导致胰岛B细胞损伤和血管并发症，但也可降低炎症和氧化应激水平。
