Maintenance ofβcell identity and functional maturation:a novel mechanism for diabetes intervention / 中华内分泌代谢杂志

ABSTRACT

The main etiology of diabetes mellitus is loss of functional β cell mass, which is responsible for the secretion of the insulin hormone to reduce elevated plasma glucose and to maintain glucose homeostasis. Type 1 diabetes has traditionally been characterized by autoimmune-mediated β-cell death leading to insulin dependence, whereas type 2 diabetes has hallmarks of peripheral insulin resistance, accompanied by β cell dysfunction, and cell death. However, a growing body of evidence suggests that β cell dysfunction and defects of functional maturation in type 2 diabetes involve (1 ) loss of cell identity, specifically proteins associated with mature cell function and transcription factors like Pdx1,MafA,Nkx6. 1,Glut2,and GK,and (2) de-differentiation,defined by regression to a progenitor or stem cell-like state. Moreover, ectopic expression of genes that are disallowed in β cells is also crucial to maintain the mature phenotype of β cells. In this review, we will combine our preliminary data and summarize the recent literature describing how β cell functional maturation is regulated. We hope that this perspective could shed some lights on possible avenues of new therapeutic intervention for diabetes mellitus.