Mibefradil通过下调FoxO1表达改善HepG2细胞的胰岛素抵抗

发布时间：2018-06-24 21:25

本文选题：Mibefradil + 胰岛素抵抗　；参考：《第三军医大学学报》2017年20期

【摘要】：目的探索Mibefradil在体外对胰岛素抵抗HepG2细胞的作用。方法将HepG2细胞分为对照组、棕榈酸盐(Palmitate,PA)诱导的HepG2细胞胰岛素抵抗模型组、药物溶剂(DMSO)组、低剂量(0.025μmol/L)Mibefradil组、高剂量(0.05μmol/L)Mibefradil组,通过检测各组糖原合成及葡萄糖消耗,观察Mibefradil对胰岛素抵抗HepG2细胞的改善作用。用qRT-PCR、Western blot检测各组Fox O1,糖异生、糖原分解限速酶,即:磷酸烯醇式丙酮酸羧基激酶(PEPCK)、葡萄糖-6-磷酸激酶(G6Pase)的mRNA、蛋白相对表达量,明确转录因子Fox O1及其靶基因的表达水平。结果相比于对照组,HepG2细胞胰岛素抵抗模型组的糖原合成量[(3.28±0.74)μg/μL vs(9.14±0.33)μg/μL,P0.01]及葡萄糖消耗量[(1.31±0.49)nmol/μg vs(5.87±2.26)nmol/μg,P0.01]明显下降;经Mibefradil干预后,胰岛素抵抗HepG2细胞的糖原合成及葡萄糖消耗得到明显改善,且高剂量组的糖原合成[(7.09±0.60)μg/μL vs(5.73±0.16)μg/μL,P0.01)]及葡萄糖消耗[(6.45±0.02)nmol/μg vs(5.61±0.29)nmol/μg,P0.01]显著高于低剂量组,表明Mibefradil可改善HepG2细胞的胰岛素抵抗。qRT-PCR及Western blot检测结果表明,胰岛素抵抗HepG2细胞的Fox O1、PEPCK、G6Pase的表达量均显著增加(P0.01);经Mibefradil干预后,其表达量呈剂量依赖性下降(P0.05)。结论Mibefradil对胰岛素抵抗HepG2细胞具有改善作用,此作用可能与下调Fox O1的表达有关。
[Abstract]:Objective to explore the effect of Mibefradil on insulin resistance HepG2 cells in vitro. Methods HepG2 cells were divided into control group, Palmitate (PA) induced insulin resistance model group, drug solvent (DMSO) group, low dose (0.025 u mol/L) Mibefradil group, high dose (0.05 mu mol/L) Mibefradil group, by detecting each group of glycogen synthase The effect of Mibefradil on the improvement of insulin resistance to HepG2 cells was observed. QRT-PCR and Western blot were used to detect Fox O1, glucoseogenesis, and glycogen decomposition rate limiting enzyme, namely, phosphoenolpyruvate carboxyl kinase (PEPCK), mRNA of glucose -6- phosphate kinase (G6Pase), relative expression of protein, and specific transcription factor Fox The target gene expression level. Compared to the control group, the glycogen synthesis of HepG2 cell insulin resistance model group was [(3.28 + 0.74) mu g/ L vs (9.14 + 0.33) mu g/ mu L, P0.01] and glucose consumption [(1.31 + 0.49) nmol/ u g vs (5.87 + 2.26) nmol/ micrg). The formation and glucose consumption were obviously improved, and the glycogen synthesis of the high dose group [(7.09 + 0.60), vs (5.73 + 0.16), g/, L, P0.01) and glucose consumption [(6.45 + 0.02) nmol/ mu g vs (5.61 + 0.29) nmol/ u g, P0.01] significantly higher than the low dose group. The results showed that the expression of Fox O1, PEPCK, G6Pase in insulin resistant HepG2 cells increased significantly (P0.01). After Mibefradil, the expression decreased in a dose-dependent manner (P0.05). Conclusion Mibefradil has an improved effect on the insulin resistance HepG2 cells, which may be related to the downregulation of Fox O1.
【作者单位】：第三军医大学新桥医院内分泌科;第三军医大学大坪医院野战外科研究所第一研究室创伤、烧伤与复合伤国家重点实验室;第三军医大学新桥医院中心实验室;第三军医大学新桥医院中西医结合科;
【基金】：国家自然科学基金面上项目(81570781)~~
【分类号】：R587.1

【相似文献】