Abstract：
Diabetes mellitus (DM) is a group of chronic metabolic disorders characterized by persistent hyperglycemia. In our study, we analyzed the level and location of RAP1 changes in the development of β-cell dysfunction induced by glucotoxicity. We employed three pancreatic β-cell lines, namely INS-1, 1.2B4, and NIT-1, as well as a streptozotocin-induced diabetes rat model. We demonstrate that after high glucose treatment, RAP1 is increased, probably through induction by AKT, allowing RAP1 to shuttle from the nucleus to the cytoplasm and activate NF-κB signaling. Furthermore, non-enzymatic post-translational modifications of RAP1, such as advanced glycation end products and carbonylation may affect the function of RAP1, such as activation of the NF-κB signaling. Taken together, we showed that RAP1 is a new player in the mechanism of glucotoxicity in pancreatic β-cells.
摘要：
糖尿病（DM）是一组以持续高血糖为特征的慢性代谢紊乱。在我们的研究中,我们分析了葡萄糖毒性诱导的β细胞功能障碍发展过程中RAP1的水平和位置变化。我们采用了三种胰腺β细胞系，即INS-1、1.2B4和NIT-1，以及链脲佐菌素诱导的糖尿病大鼠模型。我们证明，在高糖治疗后，RAP1增加，可能是通过AKT的诱导，允许RAP1从细胞核穿梭到细胞质并激活NF-κB信号传导。此外，RAP1的非酶翻译后修饰，如糖基化终产物和羰基化，可能会影响RAP1的功能，如NF-κB信号的激活。一起来看,我们表明RAP1是胰腺β细胞葡萄糖毒性机制的新参与者。
