Pu Weidong, Pan Yang, Yang Kang, Gao Jian, Tian Fen, Song Jingrui, Huang Yubing, Li Yanmei
State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, China.
Natural Products Research Center of Guizhou Province, Guizhou Medical University, Guiyang, China.
Front Pharmacol. 2025 Apr 9;16:1575450. doi: 10.3389/fphar.2025.1575450. eCollection 2025.
Traditional Chinese Medicine (TCM) theory posits that type 2 diabetes mellitus (T2DM) characterized by Qi and Yin deficiency, is associated with elevated blood lipid levels. The Xinmaitong formula (XMT) is a folk remedy believed to lower blood lipid levels. However, the functional components and molecular mechanisms through which XMT exerts its anti-diabetic effects remain to be elucidated. This study aimed to investigate the therapeutic effects and potential mechanisms of XMT in the treatment of T2DM, focusing on the glucagon-like peptide-1 receptor (GLP-1R) signaling pathway.
A TCM formula that promotes GLP-1R expression was screened using a GLP-1R promoter-dependent luciferase reporter gene vector (PGL3-GLP-1R-luc). The T2DM mouse model was established using a high-fat diet and streptozotocin (STZ). Blood glucose levels were measured using a glucometer and oral glucose tolerance test (OGTT). Serum biochemical parameters and insulin levels were also assessed. Organ pathology in mice was evaluated using hematoxylin and eosin (H&E) staining. Immunofluorescence (IF) was employed to observe changes in insulin and GLP-1R expression in the pancreas of mice. The effects of medicated serum on Min6 cell growth were examined using a methyl thiazolyl tetrazolium (MTT) assay. A Min6 cell injury model was established to detect cAMP and Ca concentrations. Ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to identify blood-absorbed components of XMT.
Luciferase reporter constructs driven by GLP-1R promoter response elements analysis identified that TCM formula XMT promoted GLP-1R expression. experiments demonstrated that XMT significantly reduced fasting blood glucose levels in T2DM mice and improved OGTT results. It also exhibited protective effects on islet tissues, notably increasing GLP-1R expression and insulin secretion in the pancreas. Biochemical markers indicated no significant adverse effects on liver or kidney function following XMT administration. After treatment with palmitic acid (PA), GLP-1R expression in Min6 cells was significantly decreased. However, treatment with XMT upregulated GLP-1R expression. Additionally, cyclic adenosine monophosphate (cAMP) and Ca exhibited substantial improvements, and the key pancreatic growth protein PDX1 was activated.
XMT exerts hypoglycemic effects by upregulating GLP-1R gene expression, enhancing GLP-1R protein synthesis, and subsequently promoting cAMP release. This process activates Ca influx in pancreatic β-cells, triggering insulin exocytosis from islet cells.
中医理论认为，以气阴两虚为特征的2型糖尿病（T2DM）与血脂升高有关。心脉通配方（XMT）是一种据信可降低血脂水平的民间疗法。然而，XMT发挥抗糖尿病作用的功能成分和分子机制仍有待阐明。本研究旨在探讨XMT治疗T2DM的疗效及潜在机制，重点关注胰高血糖素样肽-1受体（GLP-1R）信号通路。
使用GLP-1R启动子依赖性荧光素酶报告基因载体（PGL3-GLP-1R-luc）筛选促进GLP-1R表达的中药配方。采用高脂饮食和链脲佐菌素（STZ）建立T2DM小鼠模型。使用血糖仪和口服葡萄糖耐量试验（OGTT）测量血糖水平。还评估了血清生化参数和胰岛素水平。使用苏木精和伊红（H&E）染色评估小鼠的器官病理学。采用免疫荧光（IF）观察小鼠胰腺中胰岛素和GLP-1R表达的变化。使用甲基噻唑基四氮唑（MTT）法检测含药血清对Min6细胞生长的影响。建立Min6细胞损伤模型以检测cAMP和Ca浓度。采用超高效液相色谱-质谱联用（UHPLC-MS）鉴定XMT的血吸收成分。
通过GLP-1R启动子反应元件分析驱动的荧光素酶报告构建体鉴定出中药配方XMT促进GLP-1R表达。实验表明，XMT显著降低T2DM小鼠的空腹血糖水平并改善OGTT结果。它还对胰岛组织表现出保护作用，特别是增加胰腺中GLP-1R的表达和胰岛素分泌。生化指标表明，给予XMT后对肝脏或肾脏功能无显著不良影响。用棕榈酸（PA）处理后，Min6细胞中GLP-1R的表达显著降低。然而，用XMT处理上调了GLP-1R的表达。此外，环磷酸腺苷（cAMP）和Ca有显著改善，关键的胰腺生长蛋白PDX1被激活。
XMT通过上调GLP-1R基因表达、增强GLP-1R蛋白合成并随后促进cAMP释放发挥降血糖作用。这一过程激活胰腺β细胞中的Ca内流，触发胰岛细胞的胰岛素胞吐作用。
