Early senescence of pancreatic β cells induced by unfolded protein response deficiency prevents type 1 diabetes

未折叠蛋白反应缺陷诱导的胰岛β细胞早期衰老可预防1型糖尿病

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Abstract

Type 1 diabetes (T1D) is a T lymphocyte-mediated autoimmune disease caused by pancreatic β‍-cell destruction, which eventually leads to reduced insulin level and increased blood glucose level (Syed, 2022). As a multifactorial disease, T1D is characterized by a genetic predisposition associated with various environmental and cellular elements (Syed, 2022). Pancreatic β cells have long been considered the "innocent victims" in T1D pathogenesis since the pancreas is attacked by the immune cells, resulting in a process known as insulitis, in which the immune cells infiltrate pancreatic islets and secrete pro-inflammatory cytokines. However, growing evidence suggests that various β‍-cell stresses, dysfunction, and death contribute to T1D pathogenesis, as it has been observed that β‍-cell dysfunction in autoantibody-positive (Aab(+)) individuals exists long before T1D diagnosis (Evans-Molina et al., 2018).

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