Eizirik Décio L, Pasquali Lorenzo, Cnop Miriam
ULB Center for Diabetes Research, Welbio Investigator, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
Indiana Biosciences Research Institute (IBRI), Indianapolis, IN, USA.
Nat Rev Endocrinol. 2020 Jul;16(7):349-362. doi: 10.1038/s41574-020-0355-7. Epub 2020 May 12.
Loss of functional β-cell mass is the key mechanism leading to the two main forms of diabetes mellitus - type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Understanding the mechanisms behind β-cell failure is critical to prevent or revert disease. Basic pathogenic differences exist in the two forms of diabetes mellitus; T1DM is immune mediated and T2DM is mediated by metabolic mechanisms. These mechanisms differentially affect early β-cell dysfunction and eventual fate. Over the past decade, major advances have been made in the field, mostly delivered by studies on β-cells in human disease. These advances include studies of islet morphology and human β-cell gene expression in T1DM and T2DM, the identification and characterization of the role of T1DM and T2DM candidate genes at the β-cell level and the endoplasmic reticulum stress signalling that contributes to β-cell failure in T1DM (mostly IRE1 driven) and T2DM (mostly PERK-eIF2α dependent). Here, we review these new findings, focusing on studies performed on human β-cells or on samples obtained from patients with diabetes mellitus.
功能性β细胞量的丧失是导致两种主要糖尿病类型——1型糖尿病（T1DM）和2型糖尿病（T2DM）的关键机制。了解β细胞功能衰竭背后的机制对于预防或逆转疾病至关重要。两种糖尿病形式存在基本的致病差异；T1DM是免疫介导的，而T2DM是由代谢机制介导的。这些机制对早期β细胞功能障碍和最终命运有不同影响。在过去十年中，该领域取得了重大进展，主要来自对人类疾病中β细胞的研究。这些进展包括对T1DM和T2DM中胰岛形态和人类β细胞基因表达的研究、在β细胞水平上对T1DM和T2DM候选基因作用的鉴定和表征，以及内质网应激信号传导，其导致T1DM（主要由IRE1驱动）和T2DM（主要依赖PERK-eIF2α）中的β细胞功能衰竭。在此，我们综述这些新发现，重点关注对人类β细胞或从糖尿病患者获得的样本所进行的研究。
