Zhu Kui-Niu, Tian Sha-Sha, Wang Hui, Tian Yu-Shan, Gu Gui-Zhang, Qiu Yao-Yao, Zhang Lu, Yang Hong-Xia
Huzhou Institute for Food and Drug Control Huzhou 313000, China.
College of Pharmaceutical Science, Zhejiang Chinese Medical University Hangzhou 311402, China.
Zhongguo Zhong Yao Za Zhi. 2021 Sep;46(17):4488-4496. doi: 10.19540/j.cnki.cjcmm.20210527.401.
This study focused on the ameliorative effects of gypenosides(GPS) on insulin sensitivity and inflammatory factors in rats with type 2 diabetes mellitus(T2 DM) and explored their possible molecular mechanisms. After the successful establishment of T2 DM model, diabetic rats were randomly divided into four groups, including model group, GPS groups(200, 100 mg·kg(-1)) and metformin group(100 mg·kg(-1)), with healthy rats serving as the control. After 6-week intragastric administration, fasting blood glucose(FBG) and oral glucose tolerance were examined. The levels of insulin, C-peptide, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) and C-reactive protein(CRP) in serum were examined. Then the homeostasis model assessment of insulin resistance(HOMA-IR) and insulin sensitivity index(ISI) were calculated. The protein expression levels of phosphorylated insulin receptor substrate-1(p-IRS-1) and phosphorylated protein kinase B(p-Akt) in skeletal muscle were measured by Western blot, as well as those of phosphorylated inhibitor of nuclear factor-κB(NF-κB) kinase β(p-IKKβ), phosphorylated alpha inhibitor of NF-κB(p-IκBα) and phosphorylated p65 subunit of NF-κB(p-p65) in adipose tissue. The relative expression levels of glucose transporter 4(GLUT4) mRNA in skeletal muscle and NF-κB mRNA in adipose tissue were measured by qRT-PCR, and the morphological changes of pancreatic tissue were observed. Compared with the model group, the GPS groups witnessed significant decrease in FBG, marked amelioration of impaired oral glucose tolerance and significant increase in ISI. Further, the high-dose GPS group saw significantly reduced HOMA-IR, TNF-α, IL-1β and CRP, significantly increased expression levels of p-IRS-1(Tyr), p-Akt and GLUT4, and markedly inhibited p-IRS-1(Ser), p-IKKβ, p-IκBα, p-p65 and NF-κB. The concentration of CRP and the expression levels of p-IRS-1(Ser), p-IKKβ, p-IκBα and NF-κB were remarkably reduced in the low-dose GPS group. However, GPS was found less effective in the regulation of serum insulin, C-peptide and IL-6 levels and the alleviation of pancreatic islet injury. The results indicated that GPS can reduce FBG and improve insulin sensitivity in diabetic rats possibly by regulating the NF-κB signaling pathway, inhibiting inflammation, and thereby regulating the expression of key proteins in the insulin signaling pathway.
本研究聚焦于绞股蓝总皂苷（GPS）对2型糖尿病（T2 DM）大鼠胰岛素敏感性及炎症因子的改善作用，并探讨其可能的分子机制。成功建立T2 DM模型后，将糖尿病大鼠随机分为四组，包括模型组、GPS组（200、100 mg·kg⁻¹）和二甲双胍组（100 mg·kg⁻¹），以健康大鼠作为对照。经6周灌胃给药后，检测空腹血糖（FBG）及口服葡萄糖耐量。检测血清中胰岛素、C肽、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和C反应蛋白（CRP）的水平。然后计算胰岛素抵抗稳态模型评估（HOMA-IR）和胰岛素敏感性指数（ISI）。通过蛋白质免疫印迹法检测骨骼肌中磷酸化胰岛素受体底物-1（p-IRS-1）和磷酸化蛋白激酶B（p-Akt）的蛋白表达水平，以及脂肪组织中磷酸化核因子-κB（NF-κB）激酶β（p-IKKβ）、磷酸化NF-κBα抑制因子（p-IκBα）和磷酸化NF-κB p65亚基（p-p65）的蛋白表达水平。通过实时荧光定量PCR检测骨骼肌中葡萄糖转运蛋白4（GLUT4）mRNA和脂肪组织中NF-κB mRNA的相对表达水平，并观察胰腺组织的形态变化。与模型组相比，GPS组FBG显著降低，口服葡萄糖耐量受损明显改善，ISI显著升高。此外，高剂量GPS组HOMA-IR、TNF-α、IL-1β和CRP显著降低，p-IRS-1（Tyr）、p-Akt和GLUT4的表达水平显著升高，p-IRS-1（Ser）、p-IKKβ、p-IκBα、p-p65和NF-κB明显受到抑制。低剂量GPS组CRP浓度及p-IRS-1（Ser）、p-IKKβ、p-IκBα和NF-κB的表达水平显著降低。然而，发现GPS对血清胰岛素、C肽和IL-6水平的调节及胰岛损伤的减轻效果较差。结果表明，GPS可能通过调节NF-κB信号通路、抑制炎症，从而调节胰岛素信号通路关键蛋白的表达，降低糖尿病大鼠的FBG并提高胰岛素敏感性。
