2型糖尿病β细胞去分化的分子生物学机制

The Molecular Biological Mechanism ofβCell Dedifferentiation in Type 2 Diabetes

2型糖尿病是一种常见的代谢性疾病,其发病机制与胰岛β细胞功能障碍密切相关。β细胞去分化是2型糖尿病发展过程中β细胞功能和质量丧失的潜在机制。本文从分子表型水平和表观遗传学水平两个角度,讨论了最新的β细胞去分化研究进展。当前研究表明,在炎性刺激、氧化应激、内质网应激等因素的作用下,β细胞去分化涉及β细胞身份基因表达的下调、β细胞禁基因表达的上调以及祖细胞基因的刺激。这些变化导致β细胞从成熟分化状态逆转为去分化状态。此外,非编码RNA包括MiRNA和长链非编码RNA(lncRNA)也在该过程中发挥关键的中介作用,从表观遗传修饰因子的招募、转录和转录后调节,最终控制mRNA的降解。进一步研究这些机制有助于为2型糖尿病的治疗提供新的思路。

Type 2 diabetes is a common metabolic disorder whose pathogenesis is closely related to dysfunction of the pancreaticβcells.βcell dedifferentiation is a potential mechanism for the loss ofβcell function and quality during the progression of type 2 diabetes.This article discusses the latest research progress onβcell dedifferentiation from the perspectives of molecular phenotype level and epigenetic level.Current research shows thatβcell dedifferentiation involves the downregulation ofβcell identity gene expression,the upregulation ofβcell repressor gene expression,and the stimulation of progenitor gene expression in response to inflammatory stimulation,oxidative stress,and endoplasmic reticulum stress.These changes lead to the reversal ofβcells from a mature differentiated state to a dedifferentiated state.In addition,non-coding RNAs,including microRNAs and long non-coding RNAs(lncRNAs),also play a key mediating role in the process,from the recruitment of epigenetic modification factors,regulation of transcription and post-transcription,to the ultimate control of mRNA degradation.Further research on these mechanisms could provide new insights into the treatment of type 2 diabetes.