CAJ | 학술논문

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-1 s)、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±0.07比0.90±0.10)、XBP-1 s(0.41 ±0.07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5.32±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-1 s(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 ±0.11,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G6Pasc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.
목적 탐토이도소화격렬제특대2형당뇨병대서간장내질망응격화이도소민감성적영향.방법 고지음식연합련뇨좌균소건립2형당뇨병대서모형,수궤분위당뇨병조、이도소조화격렬제특조병설정상대조조.이도소조화격렬제특조분별여이중효이도소화격렬제특치료3주.검측간장면역구단백결합단백(Bip)、전절적X합결합단백1(XBP-1 s)、린산화c-Jun(p-c-Jun)、사안산린산화이도소수체저물1(p-IRS-1)、포도당6린산매(G6Pase)단백표체.결과 여정상대조조비교,당뇨병조Bip(0.28±0.07비0.90±0.10)、XBP-1 s(0.41 ±0.07비0.95 ±0.07)、p-c-Jun(0.59±0.18비1.94±0.03)、p-IRS-1(1.73 ±0.18비5.32±0.22)화G6Pase(0.11±0.01비0.45±0.01)표체균증가,P치균＜0.01.이도소화격렬제특치료후,여당뇨병조비교,이도소조화격렬제특조Bip(0.90±0.10비0.25 ±0.04화0.53 ±0.02,P치균＜0.01)、XBP-1 s(0.95 ±0.07비0.47±0.01화0.78±0.02,P＜0.01화P＜0.05)、p-c-Jun(1.94 ±0.03비0.50±0.10화1.33 ±0.11,P치균＜0.01)、p-IRS-1(5.32±0.22비1.59 ±0.32화3.13±0.02,P치균＜0.01)이급G6Pasc단백(0.45±0.01비0.15±0.02화0.25±0.01,P치균＜0.01)표체균하강,이이도소조하강경명현(P치균＜0.01).결론 이도소화격렬제특균능감경간장내질망응격、하조c-Jun안기단격매활성이급개선이도소민감성；이이도소적효응경강,제시제료강당이외,이도소가능환유항염、항양화응격혹촉사지질중분포등작용.
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 streptozotocin 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-Is in the DM group were up-regulated (0.28 ±0.07 vs 0.90 ±0.10 for Bip;0.41 ± 0.07 vs 0.95 ±0.07 for XBP-1 s; 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-1s; 1.94 ± 0.03 vs 0.50 ±0.10 for p-c-Jun; 5.32 ± 0.22 vs 1.59 ±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 ± 00.02 for Bip ; 0.95 ± 0.07 vs 0.78±0.02 for XBP-1s; 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 e-Jun N-terminal kinase activity and improved insulin sensitivity.The effect of insulin on Bip,XBP-1s,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 lipid redistribution.