维生素D缺乏对自发性糖尿病大鼠发病的影响
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摘要
目的探讨维生素D(VD)缺乏对自发性糖尿病大鼠发病的影响。方法雄性5~6周龄Zucker对照鼠及模型鼠(ZDF)按照体重随机分为4组,即正常对照组(ZL)、VD缺乏对照组(ZL+VD.Def)、模型组(ZDF)及VD缺乏模型组(ZDF+VD.Def)。各组大鼠喂养至12周龄,喂养过程中监测体重、进食量、饮水量、尿量、尿糖、血糖,并于11周龄进行口服糖耐量试验;采用HE染色观察大鼠胰岛形态结构的改变。结果 VD缺乏模型组大鼠体重明显高于模型组;饮水量及尿量增加的出现均早于模型组;VD缺乏模型组大鼠血糖升高明显早于模型组,并且各个阶段VD缺乏模型组血糖均显著高于模型组,12周龄时约为模型组的2.0倍;较模型组,VD缺乏模型组大鼠糖耐量受损、胰岛细胞损伤更为严重。结论 VD缺乏加快并加重ZDF大鼠糖尿病发病,VD缺乏是肥胖型T 2DM发病的关键因素。
Objective To investigate the effect of vitamin D( VD) deficiency on the pathogenesis of Zucker diabetic fatty( ZDF) rats. Methods Male 5-6 weeks old Zucker rats were randomly divided into 4 groups according to their body weight: normal control group( ZL),VD deficient control group( ZL + VD. Def),model group( ZDF) and VD deficient model group( ZDF + VD. Def). All the rats were fed to 12 weeks of age,and body weight,food intake,water intake,urine volume,urine glucose,fasting blood glucose were measured. The glucose tolerance was tested at 11 weeks.Pancreatic samples were taken and tissue sections were examined by pathology using HE staining. Results The body weight of ZDF + VD. Def group was higher than that of the ZDF group. Drinking water and urine volume were increased earlier than the ZDF rats. The blood glucose in the ZDF + VD. Def group was increased significantly earlier than ZDF group,it is about 2 times of the ZDF group at 12 weeks. Compared with the ZDF group,the impaired glucose tolerance and islet damage were more serious than the ZDF + VD. Def group. Conclusions Vitamin D deficiency accelerates and aggravates the pathogenesis of ZDF rats,and VD deficiency may be a key factor in the pathogenesis of obese DM Type 2.
Objective To investigate the effect of vitamin D( VD) deficiency on the pathogenesis of Zucker diabetic fatty( ZDF) rats. Methods Male 5-6 weeks old Zucker rats were randomly divided into 4 groups according to their body weight: normal control group( ZL),VD deficient control group( ZL + VD. Def),model group( ZDF) and VD deficient model group( ZDF + VD. Def). All the rats were fed to 12 weeks of age,and body weight,food intake,water intake,urine volume,urine glucose,fasting blood glucose were measured. The glucose tolerance was tested at 11 weeks.Pancreatic samples were taken and tissue sections were examined by pathology using HE staining. Results The body weight of ZDF + VD. Def group was higher than that of the ZDF group. Drinking water and urine volume were increased earlier than the ZDF rats. The blood glucose in the ZDF + VD. Def group was increased significantly earlier than ZDF group,it is about 2 times of the ZDF group at 12 weeks. Compared with the ZDF group,the impaired glucose tolerance and islet damage were more serious than the ZDF + VD. Def group. Conclusions Vitamin D deficiency accelerates and aggravates the pathogenesis of ZDF rats,and VD deficiency may be a key factor in the pathogenesis of obese DM Type 2.
引文
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[15]奚赛飞,斯徐伟,朱科燕,等.ZDF(fa/fa)大鼠的糖脂代谢特点与胰岛素抵抗特性[J].实验动物与比较医学,2014,34(2):102-106.
[16]朱超,朱莹莹,李二妮.等.糖尿病合并冠心病ZDF大鼠模型的构建[J].中国实验动物学报,2016,24(2):111-115.
[17]Leonard BL,Watson RN,Loomes KM,et al.Insulin resistance in the Zucker diabetic fatty rat:a metabolic characterisation of obese and lean phenotypes[J].Acta Diabetol,2005,42(4):162-170.
[18]Crujeiras AB,Carreira MC,Cabia B,et al.Leptin resistance in obesity:An epigenetic landscape[J].Life Sci,2015,140:57-63.
[19]Norman AW.Minireview:vitamin D receptor:new assignments for an already busy receptor[J].Endocrinology,2006,147(12):5542-5548.
[20]Berridge MJ.Vitamin D deficiency and diabetes[J].Biochem J,2017,474(8):1321-1332.
[21]Denburg MR,Bhan I.Vitamin D-binding protein in health and chronic kidney disease[J].Semin Dial,2015,28(6):636-644.
[2]Van Belle TL,Gysemans C,Mathieu C.Vitamin D and diabetes:the odd couple[J].Trends Endocrinol Metab,2013,24(11):561-568.
[3]Al-Shoumer KA,Al-Essa TM.Is there a relationship between vitamin D with insulin resistance and diabetes mellitus?[J].World J Diabetes,2015,6(8):1057-1064.
[4]Shiota M,Printz RL.Diabetes in Zucker diabetic fatty rat[J].Methods Mol Biol,2012,933:103-123.
[5]高秀莹,周迎生.2型糖尿病鼠类模型的研究进展[J].中国实验动物学报,2014,22(4):71-76.
[6]宋丹,冉丽媛,姜如娇,等.糖尿病研究中的动物模型进展[J].中国比较医学杂志,2016,26(9):83-87.
[7]Rosen CJ.Vitamin D Insufficiency[J].N Engl J Med,2011,364(3):248-254.
[8]Li YX,Zhou L.Vitamin D deficiency,obesity and diabetes[J].Cell Mol Biol(Noisy-le-grand),2015,61(3):35-38.
[9]Robinson C,Chiang M,Thompson SN,et al.Occurrence of vitamin D deficiency in pediatric patients at high risk in West Virginia[J].South Med J,2012,105(10):504-507.
[10]González-Molero I,Rojo-Martínez G,Morcillo S,et al.Hypovitaminosis D and incidence of obesity:a prospective study[J].Eur J Clin Nutr,2013,67(6):680-682.
[11]Zhang MX,Pan GT,Guo JF,et al.Vitamin D deficiency increases the risk of gestational diabetes mellitus:a meta-analysis of observational studies[J].Nutrients,2015,7(10):8366-8375.
[12]Iqbal K,Islam N,Mehboobali N,et al.Association of vitamin D deficiency with poor glycaemic control in diabetic patients[J].J Pak Med Assoc,2016,66(12):1562-1565.
[13]Afzal S,Bojesen SE,Nordestgaard BG.Low 25-hydroxyvitamin D and risk of type 2 diabetes:a prospective cohort study and meta analysis[J].Clin Chem,2013,59(2):381-391.
[14]陈小真,戎亦骊,马全鑫,等.糖尿病ZDF大鼠早期微血管并发症的生化指标及病理组织学变化[J].中国比较医学杂志,2016,26(5):63-70.
[15]奚赛飞,斯徐伟,朱科燕,等.ZDF(fa/fa)大鼠的糖脂代谢特点与胰岛素抵抗特性[J].实验动物与比较医学,2014,34(2):102-106.
[16]朱超,朱莹莹,李二妮.等.糖尿病合并冠心病ZDF大鼠模型的构建[J].中国实验动物学报,2016,24(2):111-115.
[17]Leonard BL,Watson RN,Loomes KM,et al.Insulin resistance in the Zucker diabetic fatty rat:a metabolic characterisation of obese and lean phenotypes[J].Acta Diabetol,2005,42(4):162-170.
[18]Crujeiras AB,Carreira MC,Cabia B,et al.Leptin resistance in obesity:An epigenetic landscape[J].Life Sci,2015,140:57-63.
[19]Norman AW.Minireview:vitamin D receptor:new assignments for an already busy receptor[J].Endocrinology,2006,147(12):5542-5548.
[20]Berridge MJ.Vitamin D deficiency and diabetes[J].Biochem J,2017,474(8):1321-1332.
[21]Denburg MR,Bhan I.Vitamin D-binding protein in health and chronic kidney disease[J].Semin Dial,2015,28(6):636-644.