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早期胰岛素治疗对糖尿病大鼠肝脏固醇调节级联反应和脂肪沉积的影响 被引量：10

Effects of early insulin therapy on sterol regulatory element binding protein 1 pathway and lipid accumulation in liver of type 2 diabetic rats
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摘要 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）、胞质固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（22．4g±3．6g比12．0g±2．6g，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。 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 t （Insigl）, SREBP1 and nuclear SREBP1 （nSREBP1） 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 nSREBP1 were elevated （ 1.03± 0. 14 vs 0. 41 ±0. 01 for SREBP1 ; 3.63 ±0. 77 vs 0. 96 ±0. 20 for nSREBP1, 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.
作者 孙卫平 毕艳 梁华 蔡梦茵 陈香 朱延华 叶建平 翁建平
机构地区 中山大学第三附属医院内分泌科 Pennington Biomedical Research Center
出处 《中华医学杂志》 CAS CSCD 北大核心 2011年第26期1809-1812,共4页 National Medical Journal of China
基金 国家重点基础研究发展计划“973”项目（2006CB503902）
关键词 糖尿病 2型 脂肪肝 胰岛素 固醇调节因子结合蛋白1 Diabete mellitus, type 2 Steatosis Insulin Sterol regulatory element binding protein 1
分类号 R587.1 [医药卫生—内分泌]
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同被引文献91

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中华医学杂志
2011年 第26期

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