人GLP-1(7-36)酰胺对非肥胖型糖尿病小鼠胰岛炎的影响

目的通过观察人胰高糖素样肽1（GLP-1）刺激后非肥胖型糖尿病（NOD）小鼠胰岛组织形态学的变化,研究GLP-1对NOD 1型糖尿病小鼠胰岛炎的影响。方法 GLP-1治疗组小鼠用微型渗透泵皮下持续泵入人GLP-1,对照组小鼠泵入生理盐水,4周后将其胰腺组织做HE染色、5-溴脱氧尿嘧啶核苷（Br-dU）/胰岛素双重免疫染色及导管细胞角蛋白（DCK）/胰岛素双重免疫荧光染色,观察小鼠胰岛炎的变化及胰岛β细胞的复制和胰腺导管上皮β细胞的新生。结果与对照组相比,GLP-1治疗组NOD小鼠胰岛单核细胞浸润明显减轻,胰岛炎评分明显下降（P〈0.001）。GLP-1治疗组胰岛可见较多BrdU阳性的β细胞和胰岛素阳性的导管上皮细胞,而在对照组几乎看不到。结论人GLP-1持续刺激NOD小鼠后,可使1型糖尿病小鼠胰岛炎减轻并促进β细胞再生。

The effect of continuous stimulation of human glucagon-like peptide-1(7-36) amide on insulitis in a mouse model(NOD)

【Objective】 To investigate the effect of continuous stimulation of human glucagon-like peptide-1（GLP-1）on insulitis in NOD mice by examining changes of islet histomorphology.【Methods】 The mice in the GLP-1 group and the control group were infused subcutaneously with human GLP-1 and saline respectively via a mini-osmotic pump for 4 weeks.Evaluation of insulitis score was performed by staining with haematoxylin and eosin.Beta cell proliferation of the pancreases islets and neogenesis from ducts of the pancreases were examined by 5-bromodeoxyuridine（BrdU）/insulin double immunostaining and duct cytokeratin（DCK）/insulin double immunofluorescence staining respectively.【Results】 In the GLP-1 group Mononuclear cell infiltration in the islets was lessened and insulitis scores was significantly decreased（p0.001）compared with the control group.There were more BrdU-positive beta cells and insulin-positive duct epithelium in the GLP-1 group,which can hardly been seen in the control group.【Conclusion】 Continuous infusion of human GLP-1 to prediabetic NOD mice not only lessens insulitis,but also induces beta cell regeneration.