2型糖尿病中胰岛β细胞去分化的研究进展  

Research Advances in Islet β Cells Dedifferentiation in Type 2 Diabetes

作　　者：黄蓉蓉 欧瑜[1] HUANG Rong-rong;OU Yu(School of Life Science and Technology,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京211198

出　　处：《药物生物技术》2021年第3期302-307,共6页Pharmaceutical Biotechnology

摘　　要：中国是糖尿病大国,以2型糖尿病为主。过去认为2型糖尿病中胰岛β细胞功能减退的原因是β细胞凋亡,但胰岛β细胞去分化的发现拓展了β细胞功能减退的机制。胰岛β细胞去分化后,其胰岛素分泌功能大幅下降,功能性蛋白活性丧失,基因表达发生改变。β细胞标志基因表达下降并且祖细胞标志物基因表达上调,这些基因表达变化可作为β细胞去分化的依据。代谢过负荷、重要转录因子受损、氧化环境改变、糖毒性等都可能是β细胞去分化的原因。虽然β细胞发生去分化受损,但胰岛素治疗、GLP-1类药物、SGLT-2抑制剂类药物等可通过不同方式直接促进去分化β细胞再分化,或者刺激其他细胞转分化成β细胞而改善β细胞功能减退。文章对胰岛β细胞去分化的进程、身份认定、可能机制、药物进展及研究技术进行综述,为开发2型糖尿病治疗手段及药物研究提供了新思路。China has become diabetic superpower,and type 2 diabetes is the main type. In the past,it was thought that pancreatic βcell dysfunction was resulted from β cell apoptosis,but the discovery of pancreatic β cell dedifferentiation expanded the mechanism. After the dedifferentiation,β cells dramatically decreased insulin secretion function,lost the activity of functional proteins and changed the gene expression. Dedifferentiated β cells decreased expression of β cell enriched genes,and increased expression of progenitor cell marker genes. The changes of gene expression could be used as the indicator of β cell dedifferentiation. Metabolic overload,damage of important transcription factors,changes of oxidative environment and glucotoxicity might be the possible reasons for β cell dedifferentiation. Although the dedifferentiation impaired β cell,treatments including insulin therapy,GLP-1 drugs,SGLT-2 inhibitors and some other drugs can directly promote the redifferentiation of β cells,or stimulate the transdifferentiation from other cells into β cells to attenuate β cell dysfunction. This review discusses the dedifferentiation process,β cell identity,possible mechanism and research technology of pancreatic β cell dedifferentiation,which provides a new idea for the development of treatment methods and drug research of type 2 diabetes.

关 键 词：2型糖尿病 胰岛β细胞去分化 再分化 Β细胞功能减退 β细胞标志基因 祖细胞标志物 

分 类 号：R587.1[医药卫生—内分泌]