高脂高糖饮食诱导建立2型糖尿病小型猪模型

Establish minipig model of type 2 diabetes mellitus with high-fat and high-sucrose diet

目的建立2型糖尿病小型猪模型，观察其血清中胰高血糖素样肽-1（GLP-1）的变化及其与血糖、胰岛素、C肽的关系。方法将20头4月龄中国实验用小型猪[雌雄各半，体重（16．9±1．1）kg]按数字表法随机分为两组：基础饲料组（CD组）和高脂高糖组（HFSD组），每组10头，雌雄各半。其中CD组喂食基础饲料，HFSD组喂食高脂高糖饲料，用于制作2型糖尿病小型猪模型，以空腹血糖值≥7．0mmol／L为模型制作成功。分别于实验起始起第0、3、6个月末取2组动物隔夜空腹血，测定血糖、胰岛素、C肽以及血脂；取餐后2h血，测定GLP-1。两组间数据比较采用t检验，GLP-1与其他变量的关系检验用Pearson相关分析法。结果在第6个月末HFSD组体重为（74±11）kg，CD组为（44±4）kg，组问差异有统计学意义（t=7．93，P〈0．01）；在第6个月末HFSD组空腹血糖为（7．6±1．8）mmol／L，CD组为（4．4±0．7）mmol／L，2组差异有统计学意义（t：4．32，P〈0．01），证实糖尿病动物模型成功建立。与CD组相比，在第6个月末HFSD组TG、TC均显著升高，差异均有统计学意义[分别为（0．83±0．29）、（0．56±0．18）mmol／L和（4．0±1．0）、（2．8±0．5）mmol／L，t=2．05、7．11，均P〈0．05]。HFSD组GLP一1降低趋势明显，其水平与空腹血糖呈负相关（r=-0．81，P〈0．01），与c肽呈正相关（r=0．73，P〈0．01），与胰岛素无明显相关趋势（r=0．19，P〉0．01）。结论高脂高糖6个月饲养可建立较为理想的2型糖尿病小型猪模型，其表现为体重增加、血糖升高并且血清TG、TC水平升高，GLP-1水平显著下降。

Objective To establish minipig model of type 2 diabetes mellitus with high-fat and high-sucrose diet and to observe the changes of serum glucagon-like peptide-1 （ GLP-1 ） and its relation with blood glucose, insulin and C-peptide. Methods Twenty 4-month-old Chinese experimental minipigs （ weighted （ 16. 9 ± 1.1 ） kg） were randomly assigned to the control diet group （ CD group, n = 10） and high-fat and high-sucrose diet （HFSD group, n = 10）, with 5 females and 5 males in each group, according to the random number table. CD group were fed with basic diet, and HFSD group were fed with high-fat and high-sucrose diet to establish type 2 diabetic minipig model. Fasting blood glucose≥7.0 mmol/L was set as the criterion that the type 2 diabetic minipig model were established successfully. Blood samples for plasma parameters, including blood glucose, insulin, C-peptide and blood lipid, were withdrawn from the animals separately at the end of the 0, 3rd and 6th month following an overnight fasting and 2 hours after feeding, and for detecting the blood GLP-1. The t test was performed to compare the data of the two groups. Pearson＇s correlation analysis was used to investigate the relationship between GLP-1 and the other variables. Results At the end of the 6th month, the average weight of HFSD group was （ 74 ± 11 ） kg and that of CD group was （44 ±4） kg （t =7.93,P 〈0. 01 ）. At the end of the 6th month, the concentrations of fasting blood glucose in HFSD group and CD group were （7.6 ± 1.8） mmoLCL and （4. 4±0. 7） mmol/L, respectively （t =4. 32, P 〈 0. 01 ）. Tim results confirmed that type 2 diabetic animal model was established in minipig. The level of triglyceride （TG） and total cholesterol （TC） in HFSD group （ （ 0. 83 ± 0. 29 ） and （ 4. 0 ± 1.0） mmol/L,respectively）was significantly increased compared with those in CD group （ （0. 56 ±0. 18） and （2. 8 ±0. 5） mmol/L） （t =2. 05, 7. 11, both P 〈 0. 05）. The level of GLP-1 in HFSD group had a clear tendency of decreasing, which was negatively correlated with blood glucose （ r = - 0. 81, P 〈 0. 01 ） , had a positive assoeiation with C-peptide （r = 0. 73, P 〈 0. 01 ） , and had no significant association with insulin（ r = 0. 19, P 〉 0. 01 ）. Conclusions A 6-month of feeding with high-fat and high-sucrose diet can establish an ideal type 2 diabetes model in minipig, which features weight gain, blood glucose elevation, increased levels of serum TG and TC, and significantly decreased GLP-1 level.