Wu Wen-Bin, Gao Fan, Tang Yue-Heng, Wang Hong-Zhan, Dong Hui, Lu Fu-Er, Yuan Fen
Institution of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Chin J Integr Med. 2025 Jan;31(1):39-48. doi: 10.1007/s11655-024-3915-1. Epub 2024 Nov 18.
To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β -cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine.
The db/db mice were divided into the model (distilled water), low-dose HRD (LHRD, 3 g/kg), high-dose HRD (HHRD, 6 g/kg), and liraglutide (400 µ g/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group (n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then, GLP-1, GLP-1R, prohormone convertase 1/3 (PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA), and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot, IHC, IF, and real-time quantitative polymerase chain reaction, respectively.
HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time (P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon (P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass (P<0.01). After HRD treatment, the levels of GLP-1, GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased (P<0.05 or P<0.01).
HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
通过调节胰岛和肠道中的旁分泌和内分泌胰高血糖素样肽-1（GLP-1）/GLP-1受体（GLP-1R）来维持胰岛β细胞身份，阐明黄连人参汤（HRD）改善2型糖尿病的作用。
采用随机数字表将db/db小鼠分为模型组（蒸馏水）、低剂量HRD组（LHRD，3 g/kg）、高剂量HRD组（HHRD，6 g/kg）和利拉鲁肽组（400 μg/kg），每组8只小鼠。将db/m小鼠作为对照组（n = 8，蒸馏水）。小鼠的整个治疗持续6周。使用酶联免疫吸附测定试剂盒对血液胰岛素、葡萄糖和GLP-1水平进行定量。通过免疫组织化学（IHC）和免疫荧光（IF）染色测定胰岛细胞的增殖和凋亡因子。然后，分别通过蛋白质免疫印迹法、免疫组织化学、免疫荧光和实时定量聚合酶链反应检测GLP-1、GLP-1R、激素原转化酶1/3（PC1/3）、PC2、v-maf肌腱膜纤维肉瘤癌基因同源物A（MafA）和胰腺十二指肠同源盒1（PDX1）。
HRD降低了db/db小鼠的体重和血糖，同时提高了胰岛素敏感性（P < 0.05或P < 0.01）。HRD还促进小鼠分泌更多胰岛素和更少胰高血糖素（P < 0.05或P < 0.01）。此外，它还增加了胰岛β细胞数量并减少了胰岛α细胞量（P < 0.01）。HRD治疗后，胰腺和肠道中GLP-1、GLP-1R、PC1/3、PC2、MafA和PDX1的水平显著升高（P < 0.05或P < 0.01）。
HRD可维持胰岛β细胞的正常功能和身份，其潜在机制与促进胰腺和肠道中GLP-1的旁分泌和内分泌激活有关。
