摘要
胰岛素原前体基因几乎只在胰岛β细胞表达，对维持胰岛素的分泌至关重要。葡萄糖是该基因的主要生理性调节剂。长期慢性高血糖（糖毒性）和高血脂（脂毒性）可通过抑制胰岛素原前体基因表达，促进2型糖尿病中β细胞的损伤。糖毒性涉及胰十二指肠同源盒因子-1（PDX-1）及肌腱膜纤维肉瘤癌基因同源核A（MafA）结合活性的降低以及CCAAT增强子结合蛋白（C／EβP）β活性的增强；脂毒性涉及PDX-1核转运及MafA基因表达的抑制。糖毒性与脂毒性有共同的作用靶位，联合作用对胰岛素原前体基因表达及β细胞功能损害更大。
The preproinsulin gene is expressed almost exclusively in pancreatic beta-cells. It is of great significance for the secretion of insulin. Glucose is the major physiologic regulator of insulin gene expression. Chronically elevated levels of glucose （glucotoxicity） and lipids （lipotoxicity） contribute to the worsening of beta-eel] function in type 2 diabetes via the inhibition of preproinsulin gene expression. The mechanisms of glucotoxicity involve decreased binding activities of pancreatic/duodenal homeobox-1 （ PDX- 1 ）,mammalian homologne of avian （MafA）, and increased activity of C/EBP beta. While lipotoxicity involves inhibition of PDX-1 nuclear translocation and MafA gene expression. Glucotoxicity and lipotoxicity have common targets, which make their combination particularly harmful to preproinsulin gene expression and beta-cell function in type 2 diabetes.
出处
《国际内分泌代谢杂志》
2007年第6期386-388,共3页
International Journal of Endocrinology and Metabolism
关键词
糖尿病
Β细胞
胰岛素
基因
Diabetes mellitus
β-cell
Insulin
Gene
