摘要
目的:观察胰升糖素样多肽-1(glucagon like peptide-1,GLP-1)对OLETF(O tsuka Long-Evans Tokush im a fat-ty)大鼠血糖和糖耐量的影响,及其对胰腺B细胞的保护作用。方法:将12周雄性OLETF大鼠分为GLP-1治疗和未治疗组,并以同种系非糖尿病LETO(Long-Evans Tokush im a O tsuka)大鼠为正常对照。于12,14及20周时,对所有大鼠进行口服葡萄糖耐量试验(OGTT)试验,饲养至20周时处死。对胰腺病理切片分别进行HE染色、胰岛素染色、增殖细胞核抗原染色(proliferation cell nuc lear antigen,PCNA)及凋亡细胞染色,测量胰岛B细胞的增殖率和凋亡率。用电镜观察胰岛内细胞超微结构。结果:(1)14及20周OLETF大鼠GLP-1治疗组血糖曲线下面积低于OLETF未治疗组,分别为(29.93±3.15vs.34.99±4.30,P<0.01)和(38.37±3.18vs.42.38±2.37,P<0.01)。(2)14及20周OLETF大鼠GLP-1治疗组胰岛素曲线下面积高于OLETF未治疗组,分别为(10.86±1.56vs.9.07±1.28,P<0.01)和(13.00±1.50vs.10.35±0.86,P<0.01)。(3)20周龄GLP-1治疗组OLETF大鼠胰岛内胰岛素含量以及胰岛中B细胞数量增加,B细胞超微结构改善。胰岛B细胞的增殖率增加(48.9±39.6vs.39.6±9.3,P<0.05),凋亡率下降(24.8±4.2vs.30.8±5.8,P<0.01)。结论:GLP-1能够通过促进胰岛B细胞增殖抑制其凋亡,增加胰岛B细胞数目,改善B细胞内分泌颗粒的形态,从而改善2型糖尿病大鼠的糖耐量。
Objective： To investigate the effect of GLP-1 on the blood glucose in type 2 diabetic rats, and its protective effects on the islet B cells. Methods： Thirty rats were divided into three groups：spontaneous type 2 diabetes animal model OLETF rats ,GLP-1 [ from the twelfth week 56μg/（ kg·d）, sc ] therapy group and LETO rats as control. In the 14th and 20th weeks, standard OGTr including fast and 2 h-plasma glucose were measured respectively. In the 14th weeks, 3 rats from each group were killed randomly, and the rest of the rats were killed until the 20th week. Immunostaining with the marker of PCNA, TUNEL, and insulin assessed metabolic changes in the islet. Ultrastructure of the B cell was ob- served with the electronic microscope. Results： In the 14th and 20th week, AUC for insulin were higher in treated animals（10.86 ± 1.56 vs. 9.07 ±1.28,P〈0.01）and （13.00±1.50 vs. 10.35 ±0.86,P〈0.01 ）, which was paralleled by a decrease in AUC for glucose, （29.93 ±3.15 vs. 34.99 4.30, P〈0.01 ）and （38.37±3.18 vs. 42.38±2.37 ,P〈0.01 ）. Ex vivo immunostaining with the marker of cell proliferation, PCNA, showed that the metabolic changes observed in rats treated with GLP-1 were associated with an increase in cell proliferation of the B cell（48.9 ± 39.6 vs. 39.6 ± 9.3 ,P〈0.05 ）. TUNEL staining, a marker of cellular apoptosis, indicated a reduction of apoptotic cells within the islet in GLP-1- treated rats（24.8±4.2 vs. 30.8±5.8 ,P〈0.01 ）. Immunostaining for the insulin showed a significant increase in insulin content in GLP-1-treated animals. GLP-l-treatment ameliorated the ultrastructure of the B cell. Conclusion： Our findings have provided evidence that the beneficial effects of GLP-1 in OLETF rats are mediated by an increase in islet cell proliferation and a decrease of cellular apoptosis.
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2006年第4期375-380,共6页
Journal of Peking University:Health Sciences
