CAJ | 학술논문

目的探讨早期胰岛素治疗对2型糖尿病大鼠肝脏固醇调节级联反应和脂肪沉积的影响.方法高脂饮食联合小剂量链脲佐菌素诱导成2型糖尿病大鼠模型,分为糖尿病组(DM)和早期胰岛素治疗组(INS).INS组大鼠给予低精蛋白锌人胰岛素治疗3周.Western印迹检测肝脏免疫球蛋白结合蛋白(Bip)、胰岛素诱导基因1(Insig1)、氧调节蛋白150(ORP150)、胞质同醇调节因子结合蛋白1(SREBP1)和核SREBP1(nSREBP1)蛋白表达.结果与正常大鼠比较,DM组Bip和ORP150蛋白表达增加(Bip:0.67±0.02比0.43±0.01;ORP150:1.83±0.03比1.04±0.03,均P<0.05),Insig1蛋白表达下调(0.25±0.02比0.80±0.07,P<0.05),SREBP1和nSREBP1蛋白表达均增加(SREBP1∶1.03±0.14比0.41±0.01;nSREBP1:3.63±0.77比0.96±0.20,均P<0.05).胰岛素治疗后Bip和ORP150蛋白表达减少(Bip:0.41±0.04比0.67±0.02;ORP150:1.11 ±0.04比1.83±0.03,均P<0.05),Insig1蛋白表达上调(0.43 ±0.02比0.25±0.02,P<0.05),SREBP1和nSREBP1蛋白表达均降低(SREBP1:0.46±0.01比1.03±0.14;nSREBP1:1.65±0.18比3.63±0.77,P<0.05).胰岛素治疗增加大鼠内脏脂肪重量(22.4 g±3.6 g比12.0 g±2.6 g,P<0.05).结论早期胰岛素治疗诱导肝脏脂质向内脏脂肪组织重新分布,内质网应激减轻和SREBP1表达及其活性下调可能是胰岛素降低肝脏异位脂质沉积的分子机制之一.
목적 탐토조기이도소치료대2형당뇨병대서간장고순조절급련반응화지방침적적영향.방법 고지음식연합소제량련뇨좌균소유도성2형당뇨병대서모형,분위당뇨병조(DM)화조기이도소치료조(INS).INS조대서급여저정단백자인이도소치료3주.Western인적검측간장면역구단백결합단백(Bip)、이도소유도기인1(Insig1)、양조절단백150(ORP150)、포질동순조절인자결합단백1(SREBP1)화핵SREBP1(nSREBP1)단백표체.결과 여정상대서비교,DM조Bip화ORP150단백표체증가(Bip:0.67±0.02비0.43±0.01;ORP150:1.83±0.03비1.04±0.03,균P<0.05),Insig1단백표체하조(0.25±0.02비0.80±0.07,P<0.05),SREBP1화nSREBP1단백표체균증가(SREBP1∶1.03±0.14비0.41±0.01;nSREBP1:3.63±0.77비0.96±0.20,균P<0.05).이도소치료후Bip화ORP150단백표체감소(Bip:0.41±0.04비0.67±0.02;ORP150:1.11 ±0.04비1.83±0.03,균P<0.05),Insig1단백표체상조(0.43 ±0.02비0.25±0.02,P<0.05),SREBP1화nSREBP1단백표체균강저(SREBP1:0.46±0.01비1.03±0.14;nSREBP1:1.65±0.18비3.63±0.77,P<0.05).이도소치료증가대서내장지방중량(22.4 g±3.6 g비12.0 g±2.6 g,P<0.05).결론 조기이도소치료유도간장지질향내장지방조직중신분포,내질망응격감경화SREBP1표체급기활성하조가능시이도소강저간장이위지질침적적분자궤제지일.
Objective To explore the effect of early insulin therapy on sterol regulatory element binding protein 1 ( SREBP1) pathway and lipid accumulation in liver of type 2 diabetic rats ( DM ). Methods A high-fat diet plus a low-dose of streptozotocin (STZ) was administered to the Sprague-Dawley (SD) rats to create a type 2 diabetic animal model. Then the rats were divided into 3 groups: normal control ( NC) , DM (untreated diabetic rats) and INS (a 3-week treatment of NPH insulin initiated from day 3 of STZ injection). Insulin was delivered daily by a 3-week subcutaneous injection (6-8 U/day) . Liver homogenate was prepared. The protein levels of ER stress marker immunoglobulin binding protein ( Bip),oxygen-regulated protein 150 (ORP150) , insulin-induced gene 1 (Insig1) , SREBP1 and nuclear SREBP1 (nSREBPl) were assayed by Western blot. Adipose tissue mass was measured. Results In the DM group,ER (endoplasmic reticulum) stress marker Bip and ORP150 were up-regulated (0.67 ±0.02 vs 0.43 ±0. 01 for Bip; 1. 11 ±0. 04 vs 1. 83 ±0. 03 for ORP150, P <0. 05 for both) and Insigl decreased (0. 25 ±0. 02 vs 0. 80 ± 0. 07, P < 0. 05). And the expressions of SREBP1 and nSREBPl were elevated (1. 03 ±0. 14 vs 0. 41 ± 0.01 for SREBP1; 3. 63 ± 0. 77 vs 0. 96 ± 0. 20 for nSREBPl, P < 0. 05 for both) in comparison with the normal control rats. In the INS group, all aforementioned changes became attenuated or reversed (0.41 ±0.04 vs 0. 67 ±0. 02 for Bip; 1. 83 ±0. 03 vs 1. 11 ±0. 04 for ORP150; 0. 43 ±0.02 vs 0. 25 ± 0. 02 for Insigl; 0. 46 ± 0.01 vs 1. 03 ± 0. 14 for SREBP1; 1.65 ± 0. 18 vs 3. 63 ± 0. 77 for nSREBP1, P <0.05 for all). Furthermore, adipose tissue mass increased (22. 4 g ±3. 6g vs 12.0 g ±2. 6 g, P<0. 05). Conclusion The early insulin therapy induces a fat redistribution from liver to adipose tissue. The mechanism is probably through a reduction of ER stress and a down-regulated pathway of SREBP1 in liver of diabetic rats.