PDF(Pubmed)
Abstract：
Type 2 diabetes (T2D) is a polygenic metabolic disorder characterized by insulin resistance in peripheral tissues and impaired insulin secretion by the pancreas. While the decline in insulin production and secretion was previously attributed to apoptosis of insulin-producing β-cells, recent studies indicate that β-cell apoptosis rates are relatively low in diabetes. Instead, β-cells primarily undergo dedifferentiation, a process where they lose their specialized identity and transition into non-functional endocrine progenitor-like cells, ultimately leading to β-cell failure. The underlying mechanisms driving β-cell dedifferentiation remain elusive due to the intricate interplay of genetic factors and cellular stress. Understanding these mechanisms holds the potential to inform innovative therapeutic approaches aimed at reversing β-cell dedifferentiation in T2D. This review explores the proposed drivers of β-cell dedifferentiation leading to β-cell failure, and discusses current interventions capable of reversing this process, thus restoring β-cell identity and function.
摘要：
2型糖尿病（T2D）是一种多基因代谢疾病，其特征是外周组织中的胰岛素抵抗和胰腺的胰岛素分泌受损。虽然胰岛素产生和分泌的下降以前归因于产生胰岛素的β细胞的凋亡，最近的研究表明糖尿病患者的β细胞凋亡率相对较低。相反，β细胞主要经历去分化，在这个过程中，它们失去了专门的身份，并转变为无功能的内分泌祖细胞样细胞，最终导致β细胞衰竭。由于遗传因素和细胞应激的复杂相互作用，驱动β细胞去分化的潜在机制仍然难以捉摸。了解这些机制有可能为旨在逆转T2D中β细胞去分化的创新治疗方法提供信息。这篇综述探讨了β细胞去分化导致β细胞衰竭的拟议驱动因素，并讨论了能够逆转这一过程的当前干预措施，从而恢复β细胞的身份和功能。
