摘要
目的探讨胰岛素和格列齐特对2型糖尿病大鼠肝脏内质网应激和胰岛素敏感性的影响。方法高脂饮食联合链脲佐菌素建立2型糖尿病大鼠模型，随机分为糖尿病组、胰岛素组和格列齐特组并设正常对照组。胰岛素组和格列齐特组分别予以中效胰岛素和格列齐特治疗3周。检测肝脏免疫球蛋白结合蛋白（Bip）、剪切的x盒结合蛋白1（XBP-1s）、磷酸化c-Jun（p-c-Jun）、丝氨酸磷酸化胰岛素受体底物1（p-IRS-1）、葡萄糖6磷酸酶（G6Pase）蛋白表达。结果与正常对照组比较，糖尿病组Bip（0．28-4-0．07比0．90±0．10）、XBP-1s（0．41±O．07比0．95±0．07）、p-c-Jun（0．59±0．18比1．94±0．03）、p-IRS-1（1．73±0．18比5．324-0．22）和G6Pase（0．11±0．01比0．45±0．01）表达均增加，P值均〈0．01。胰岛素和格列齐特治疗后，与糖尿病组比较，胰岛素组和格列齐特组Bip（0．90±0．10比0．25±0．04和0．53±0．02，P值均〈0．01）、XBP-1s（0．95±0．07比0．47±0．01和0．78±0．02，P〈0．01和P〈0．05）、P-c-Jun（1．94±0．03比0．50±0．10和1．33±-O．11，P值均〈0．01）、p-IRS-1（5．32±0．22比1．59±0．32和3．13±0．02，P值均〈0．01）以及G6Pase蛋白（0．45±0．01比0．15±0．02和0．25±0．01，P值均〈0．01）表达均下降，以胰岛素组下降更明显（P值均〈0．01）。结论胰岛素和格列齐特均能减轻肝脏内质网应激、下调c-Jun氨基端激酶活性以及改善胰岛素敏感性；以胰岛素的效应更强，提示除了降糖以外，胰岛素可能还有抗炎、抗氧化应激或促使脂质重分布等作用。
Objective To investigate the effect of insulin and gliclazide therapy on endoplasmic reticulum （ER） stress and insulin sensitivity in the liver of type 2 diabetic rats. Methods A high fat diet plus a low-dose of streptozotoein was implemented to create a type 2 diabetic rats which were randomly divided into diabetes mellitus （DM） group, insulin treatment （INS） group and gliclazide treatment （GT） group; and healthy rats were as normal control group. Diabetic rats in INS and GT groups were given neutral protamine hagedorn （ NPH ） insulin and gliclazide respectively for 3 weeks. Protein expression levels of immunoglobulin binding protein （Bip）, spliced X-box binding protein 1 （XBP-ls）, phosphorylated c-Jun on serine 73 （p-c-Jun）, phosphorylated insulin receptor substrate 1 on serine 307 （p-IRS-1）, and glucose- 6-phosphatase （G6Pase） in liver homogenate were detected by Western blotting. Results Compared with the normal rats, Bip and XBP-ls in the DM group were up-regulated （0. 28±0. 07 vs 0. 90±0. 10 for Bip; O. 41±0. 07 vs 0. 95±0. 07 for XBP-ls; both P 〈0. 01 ） ; p-c-Jun （0. 59±0. 18 vs 1.94±0. 03）, p-IRS-1 （1.73±0. 18 vs 5.32±0. 22 ） and G6Pase（0. 11±0. 01 vs 0. 45±0. 01 ） were increased （all P values 〈 0. 01 ）. In the INS group, all of aforementioned changes were reversed （0. 90±0. 10 vs 0. 25±0. 04 for Bip; 0.95±0.07 vs 0.47±0.01 for XBP-ls; 1.94±0.03 vs 0.50±0. 10 for p-c-Jun; 5.32±0.22 vs1.59±0. 32 for p-IRS-1 ; 0.45± 0. 01 vs 0. 15 ＋ 0. 02 for G6Pase, all P values 〈 0. 01 ）. In the GT group, all of aforementioned changes were also attenuated （0. 90±0. 10 vs 0. 53±0. 02 for Bip; 0. 95±0. 07 vs 0.78＋0.02 for XBP-ls; 1.94±0.03 vs 1.33±0. 11 for p-c-Jun; 5.32±0.22 vs 3.13±0.02 for p-IRS-1; 0.45±0.01 vs 0.25±0.01 for G6Pase, all P values 〈 0.05） . Furthermore, all of aforementioned protein levels were down-regulated more obviously in the INS group comparing to the GT group （ all P values 〈 0.01 ）. Conclusions Both insulin and gliclazide therapy could relieve ER stress and c-Jun N-terminal kinase activity and improved insulin sensitivity. The effect of insulin on Bip, XBP-1 s, p-c-Jun, p-IRS-1 and G6Pase protein expressions is more obvious than that of glilcazide, which indicates besides lowering glucose, insulin might have protective effects of anti-inflammation, anti-oxidative stress or stimulation of lioid redistribution.
出处
《中华内科杂志》
CAS
CSCD
北大核心
2012年第8期638-641,共4页
Chinese Journal of Internal Medicine
基金
国家重点基础研究发展计划基金
关键词
胰岛素
糖尿病
2型
内质网
应激
胰岛素敏感性
Insulin
Diabetes mellitus, type 2
Endoplasmic reticulum
Stress
Insulinsensitivity
