艾塞那肽对糖尿病大鼠脂肪细胞脂代谢的影响

Effects of exenatide on lipid metabolism of adipose tissue in diabetic rats

目的观察比较艾塞那肽和甘精胰岛素治疗对糖尿病大鼠脂肪细胞脂代谢的影响。方法7～8周龄雄性sD大鼠，体重180～200g，按随机数字表法分为2组（对照组8只，高脂组30只）：对照组仅予普通饮食，高脂组予高脂喂养5周，联合小剂量链脲佐菌素（STZ）诱导糖尿病SD大鼠模型，3d后将成模大鼠随机分为3组进行不同干预：对照组和糖尿病组给予生理盐水，另外2组分别予艾塞那肽或甘精胰岛素干预4周。通过Westernblotting和实时定量聚合酶链式反应检测大鼠附睾周围脂肪组织中脂肪细胞脂质合成酶如磷酸烯醇式丙酮酸羧激酶（PEPCK）、脂肪酸合成酶（FAS）、乙酰辅酶A羧化酶-1（ACC-1）蛋白及基因表达，以及脂质水解相关酶如脂肪组织甘油三酯脂酶（ATGL）、色素上皮衍生因子（PEDF）基因表达。多组定量资料间比较采用方差分析，两两比较采用最小差异显著性分析。结果与对照组比较，糖尿病大鼠脂肪细胞脂质合成酶PEPCK和FAS基因及蛋白表达降低，ACC-1基因水平降低，脂质水解相关蛋白ATGL和PEDF基因表达升高（均P〈0．05）。艾塞那肽及甘精胰岛素治疗后，PEPCK、FAS基因及蛋白水平升高，ACC-1基因表达增加，ATGL、PEDF基因表达降低（均P〈0．05）。与甘精胰岛素组比较，艾塞那肽组PEPCK、FAS基因[艾塞那肽与甘精胰岛素：PEPCKmRNA（1．68±0．45）VS（1．15±0．24）；FASmRNA（7．12±0．13）vs（1．18±0．16）]及蛋白[PEPCK（1．11±0．08）vs（0．87±0．08）；FAS（1．95±0．10）VS（0．99±0．08）]水平明显升高（t=2．525、69．374、5．312、18．670，均P〈0．05）。结论艾塞那肽可促进脂肪组织甘油三酯合成、减少脂质分解，其作用强于甘精胰岛素。

Objective To investigate the mechanisms of exenatide and insulin glargine in regulating lipid metabolism of adipose tissue in diabetic rats. Methods Male SD rats （7 -8 weeks old, 180 -200 g） were randomly divided into normal chow （ NC group, n = 8 ） or high-fat diet （ n = 30）. After 5 weeks of high- fat diet, diabetic rats were induced by low dose streptozotocin （ STZ ） and were randomly divided into 3 groups： untreated diabetic group （DM）, exenatide - treated group （EXE group） or insulin glargine - treated group （INS group）. NC and DM groups were administrated by normal saline, the other two groups were given exenatide or insulin glargine for 4 weeks initiated at the 3rd day after STZ injection. Protein expressions of phosphoenolpyruvate carbexykinase （PEPCK） and fatty acid synthase （FAS） were assayed by Western blotting. Gene expressions of PEPCK, FAS, acetyl-coA carboxylasel （ACC-1）, pigment epithelium-derived factor （PEDF）, and adipose triglyceride lipase （ATGL） were quantified by real-time polymerase chain reaction（PCR）. ANOVA or LSD test were used for data analysis. Results Compared with NC group, the gene and protein levels of PEPCK, FAS, and ACC-1 in DM group were significantlydecreased （ all P 〈 0. 05 ） , while the gene expressions of ATGL and PEDF were increased （ all P 〈 0. 05 ）. After exenatide and insulin glargine treatment, mRNA and protein levels of PEPCK, FAS, and ACC-1 were increased （ all P 〈 0. 05）, and mRNA levels of ATGL and PEDF were decreased （ all P 〈 0. 05 ）. Compared with INS group, the increases in the gene and protein levels of PEPCK and FAS in EXE group were greater （PEPCK mRNA with EXE vs INS group： 1.68 ±0. 45 vs 1.15 ±0. 24; FAS mRNA： 7.12 ±0. 13 vs 1.18 ±0.16; PEPCK protein （1.11 ±0.08） vs （0.87 ±0.08）, FAS protein （1.95 ±0.10） vs （ 0.99 ± 0.08） , t =2.525, 69.374, 5.312, 18.670, all P〈0.05）. Conclusions Exenatide and insulin glargine treatment can ameliorate ectopic lipid deposition by increasing lipid synthesis and decreasing lipolysis of adipocytes in diabetic rats, in whieh exenatide has greater effect on triglyceride synthesis.