Medical experiment center, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
Toxicology Centre, University of Saskatchewan, Saskatoon, S7N 5B3, Canada.
BMC Complement Med Ther. 2022 Jul 20;22(1):193. doi: 10.1186/s12906-022-03674-2.
The traditional Chinese medicine Gegen Qinlian Decoction (GQD), as well as metformin, had been reported with anti-diabetic effects in clinical practice.
To verify whether these two medicines effectively ameliorate hyperglycemia caused by deficiency of islet β-cell mass which occurs in both type 1 and type 2 diabetes.
SD rats were injected with a single dose of STZ (55 mg/kg) to induce β-cell destruction. The rats were then divided into control, diabetes, GQD and metformin group. GQD and metformin groups were administered with GQD extract or metformin for 6 weeks. The islet α-cell or β-cell mass changes were tested by immunohistochemical and immunofluorescent staining. The potential targets and mechanisms of GQD and metformin on cell proliferation were tested using in silico network pharmacology. Real-time PCR was performed to test the expression of islet cells related genes and targets related genes.
Both GQD and metformin did not significantly reduce the FBG level caused by β-cell mass reduction, but alleviated liver and pancreas histopathology. Both GQD and metformin did not change the insulin positive cell mass but increased α-cell proliferation of the diabetic rats. Gene expression analysis showed that GQD and metformin significantly increased the targets gene cyclin-dependent kinase 4 (Cdk4) and insulin receptor substrate (Irs1) level.
This research indicates that GQD and metformin significantly increased the α-cell proliferation of β-cell deficiency induced diabetic rats by restoring Cdk4 and Irs1 gene expression.
中药葛根芩连汤（GQD）和二甲双胍在临床上均有降血糖作用。
验证这两种药物是否能有效改善 1 型和 2 型糖尿病中胰岛β细胞质量减少引起的高血糖。
SD 大鼠单次注射 STZ（55mg/kg）诱导β细胞破坏。然后将大鼠分为对照组、糖尿病组、GQD 组和二甲双胍组。GQD 组和二甲双胍组分别给予 GQD 提取物或二甲双胍治疗 6 周。通过免疫组织化学和免疫荧光染色检测胰岛α细胞或β细胞质量变化。通过计算机网络药理学测试 GQD 和二甲双胍对细胞增殖的潜在靶点和机制。实时 PCR 检测胰岛细胞相关基因和靶基因相关基因的表达。
GQD 和二甲双胍均不能显著降低β细胞质量减少引起的 FBG 水平，但能改善肝胰腺组织病理学。GQD 和二甲双胍均未改变胰岛素阳性细胞质量，但增加了糖尿病大鼠的α细胞增殖。基因表达分析表明，GQD 和二甲双胍显著增加了细胞周期蛋白依赖性激酶 4（Cdk4）和胰岛素受体底物 1（Irs1）靶基因的水平。
本研究表明，GQD 和二甲双胍通过恢复 Cdk4 和 Irs1 基因表达，显著增加了β细胞缺乏诱导的糖尿病大鼠的α细胞增殖。
