尼克酰胺-N-甲基转移酶在链脲佐菌素致糖尿病猴胰岛中的高表达及意义  

Increased expression and possible roles of nicotinamide N-methyltransferase in pancreatic islets of STZ-induced diabetic monkeys

作　　者：牟波[1] 杨志红[1] 赵家伟[1] 王宣春[1] 董雪红[1] 刘瑜[1] 胡仁明[1] 

机构地区：[1]复旦大学附属华山医院内分泌科复旦大学内分泌糖尿病研究所,上海200040

出　　处：《中国病理生理杂志》2007年第5期888-892,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金重点资助项目(No.30230380);国家863子课题资助项目(No.2002BA711A05);国家973子课题资助项目(No.2002CB713703)

摘　　要：目的:本文旨在明确尼克酰胺-N-甲基转移酶(NNMT)在链脲佐菌素(STZ)致糖尿病猴胰腺中的表达及其定位,进而分析NNMT在β细胞损伤中的重要作用。方法:应用基因芯片技术筛选STZ致糖尿病猴胰腺组织差异表达基因,选择NNMT作为研究对象。半定量RT-PCR及Western印迹法分别从mRNA及蛋白水平验证该差异,然后应用免疫组化技术观察该蛋白在胰腺内外分泌细胞中的表达情况。结果:NNMT在正常猴胰腺中仅有微弱表达,但在STZ致糖尿病猴胰腺中其mRNA及蛋白水平均明显上调。免疫组化结果显示该差异表达主要表现在胰岛β细胞分布区。结论:NNMT可以催化对维持细胞功能极为重要的尼克酰胺甲基化,其在糖尿病β细胞内表达上调可能会引起细胞内能量代谢障碍而导致β细胞损伤。AIM： To verify and localize the expression of nicotinamide N - methyltransferase （NNMT） in pan- creas of streptozotocin（STZ） -induced diabetic monkeys and understand its important role in β-cell destruction in the pathogenesis of diabetes. METHODS： Through an olig - microarray gene chip, NNMT was identified as the most obviously up - regulated genes in pancreas of STZ - induced diabetic monkeys versus controls. Semiquantitative RT - PCR and Western blotting were performed to verify the differential expression at mRNA and protein level respectively. Then the cellular localization of NNMT expression within pancreas was identified by immunohistochemical（IHC） staining. RESULTS： An obvious high expression of NNMT at both mRNA and protein levels was shown in pancreas of STZ - induced diabetic monkeys compared to that of controls. Further localization of the protein by IHC staining in pancreas specimens showed that its altered expression was restricted to central islets, most of which were β cells. CONCLUSION ： Expression of NNMT is increased in islets of STZ - induced diabetic monkeys, which infers that NNMT might participate in the process of β cell damage in diabetes probably through the mechanism of energy metabolism disturbance.

关 键 词：尼克酰胺-N-甲基转移酶 链脲菌素 糖尿病 

分 类 号：R587.1[医药卫生—内分泌]