人GLP-1(7-36)酰胺对非肥胖型糖尿病小鼠胰岛β细胞凋亡的影响

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

目的探讨人胰高糖素样肽1(GLP-1)对非肥胖型糖尿病(NOD)小鼠胰岛β细胞凋亡的影响。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、TUNEL/胰岛素双重免疫荧光染色,显微镜下观察小鼠胰岛炎的变化及胰岛β细胞的凋亡情况。结果与对照组相比,GLP-1治疗组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)。在对照组小鼠胰腺组织切片中观察到较多凋亡β细胞,而在GLP-1治疗组却很少见到。GLP-1治疗组小鼠胰岛β细胞凋亡率与对照组小鼠相比明显下降(0.07±0.01%vs0.26±0.02%,P<0.001)。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抑制β细胞凋亡。

[ Objective ] To investigate the effect of continuous stimulation of human glueagon-like peptide-l（GLP-1） on beta cell apoptosis in non-obese diabetic（NOD）mice. [ 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 apoptosis was detected by TUNEL/ insulin double immunofluorescence staining. [ Resluts ] In the GLP-1 group Mononuclear cell infihration in the islets was lessened and insulitis scores was significantly decreased（P〈0.001）compared with the control group. We observed a greater number of insulin-positive apoptotic ceils in the pancreatic sections from the control group mice than that from the GLP- 1 group mice. The percentage of apoptotic beta cells was significantly lower in the GLP- 1 group compared with the control group（0.07 ± 0.01% vs 0.26 ± 0.02%, P〈0.001）. [ Conclusions ] Continuous infusion of human GLP-1 to prediabetic NOD mice not only lessens insulitis, but also inhibits beta cell apoptosis.