利拉鲁肽对2型糖尿病大鼠的保护作用

Protective Effect of liraglutide on type 2 diabetic rats

目的探讨利拉鲁肽对胰岛素抵抗(IR)2型糖尿病大鼠模型的影响,并分析其与胰岛素受体底物-1(IRS-1)/磷脂酰肌醇3-激酶(PI3K)/葡萄糖转运蛋白4(GLUT4)信号通路的相关性。方法用高糖高脂饲料喂养联合35 mg·kg^-1链脲佐菌素(STZ)建立2型糖尿病大鼠大鼠模型;另选大鼠普通喂食作为对照组。按照给药不同将造模成功大鼠分为对照组(生理盐水)、模型组(生理盐水)、阳性对照组(0.36 mg·kg^-1罗格列酮)和低、高剂量实验组(0.2,0.4 mg·kg^-1利拉鲁肽),每组8只;均灌胃给药,连续给药4周。计算胰岛素抵抗指数(HOMA-IR),用蛋白质印迹法检测IRS-1、磷脂酰肌醇3-激酶p85亚基(PI3Kp85)、磷酸化蛋白(p-AKT)及GLUT4的表达水平。结果对照组、模型组、阳性对照组、低、高剂量实验组的HOMA-IR分别为0.14±0.02,1.59±0.16,0.62±0.03,0.80±0.06和0.42±0.04;IRS-1蛋白表达水平分别为2.82±0.19,0.72±0.05,1.11±0.13,1.11±0.06和2.17±0.12;PI3Kp85蛋白表达水平分别为2.18±0.28,0.54±0.05,1.26±0.12,1.20±0.14和2.03±0.16;p-AKT蛋白表达水平分别为2.20±0.17,0.82±0.13,1.77±0.18,1.61±0.24和1.71±0.27;GLUT4蛋白表达水平分别为1.05±0.02,0.35±0.02,1.33±0.10,0.86±0.15和1.32±0.14。上述指标,对照组、低、高剂量实验组分别与模型组比较,差异均有统计学意义(均P<0.05)。结论利拉鲁肽可通过IRS-1/PI3K/GLUT4信号通路改善2型糖尿病大鼠胰岛素抵抗。

Objective To explore the effect of liraglutide on type 2 diabetic rats with insulin resistance(IR), and to analyze its relationship to insulin receptor substrate-1(IRS-1)/phosphatidylinositol 3-kinase(PI3 K)/glucose transporter 4(GLUT4) signaling pathway. Methods The SD rats were fed with high-sugar and high-fat diet combined with 35 mg·kg^-1 streptozotocin(STZ,) to establish type 2 diabetic rat with IR model. The other rats were fed with normal feeding as control group. After making the model successfully, rats were randomly divided into control group(normal saline), model group(normal saline), active control group(0.36 mg·kg^-1 rosiglitazone) and test-L/-H group(0.2, 0.4 mg·kg^-1 liraglutide), each group had 8 rats;all rats were given treatment by intragastric administration for 4 weeks. Homeostatic Model Assessment for Insulin Resistance(HOMA-IR) was calculated. The expression levels of IRS-1, phosphatidylinositol 3-kinase p85 subunit(PI3 Kp85), phosphorylated protein(p-AKT) and GLUT4 were detected by Western blot. Results The HOMA-IR in control group,model group,active control group and test-L/-H group were 0. 14 ± 0. 02,1. 59 ± 0. 16,0. 62 ± 0. 03,0. 80 ± 0. 06,0. 42 ± 0. 04;the expression levels of IRS-1 were 2. 82 ± 0. 19,0. 72 ± 0. 05,1. 11 ± 0. 13,1. 11 ± 0. 06 and2. 17 ± 0. 12;PI3 Kp85 were 2. 18 ± 0. 28,0. 54 ± 0. 05,1. 26 ± 0. 12,1. 20 ± 0. 14 and 2. 03 ± 0. 16;p-AKT were2. 20 ± 0. 17,0. 82 ± 0. 13,1. 77 ± 0. 18,1. 61 ± 0. 24 and 1. 71 ± 0. 27;GLUT4 were 1. 05 ± 0. 02,0. 35 ± 0. 02,1. 33 ± 0. 10,0. 86 ± 0. 15 and 1. 32 ± 0. 14. There were significant differences of the factors between model group and control group or high-dose liraglutide group and model group(all P < 0. 05). Conclusion Liraglutide can improve insulin resistance in type 2 diabetic rats through the IRS-1/PI3K/GLUT4 signaling pathway.