GSK-3β mediates dexamethasone-induced pancreatic β cell apoptosis.
GSK-3β mediates dexamethasone-induced pancreatic β cell apoptosis.
复制标题
GSK-3β介导地塞米松诱导的胰腺β细胞凋亡
DOI：
10.1016/j.lfs.2015.11.017
复制
发表时间：
2016-01-01
期刊：
影响因子：
6.1
通讯作者：
Men X
中科院分区：
文献类型：
--
作者：
Guo B;Zhang W;Xu S;Lou J;Wang S;Men X
糖皮质激素，如地塞米松，是广泛使用的抗炎药。它们的使用经常与类固醇相关糖尿病的发展有关。胰腺β细胞功能障碍已被认为是类固醇相关性糖尿病的主要原因之一。然而，该机制尚未完全理解。糖原合成酶激酶-3 β（Glycogen synthase kinase-3β，GSK-3β）是一种多功能丝氨酸/苏氨酸激酶，在能量代谢、细胞生长和凋亡中起重要作用。因此，本研究确定GSK-3β在地塞米松诱导的胰腺β细胞凋亡中的作用。测定地塞米松处理对大鼠胰腺β细胞系（INS-1）凋亡（通过TUNEL和流式细胞术测定）、反应性氧化应激（ROS）产生和GSK-3β磷酸化状态的影响。GSK-3β受体-氯化锂（LiCl）对地塞米松诱导的胰岛β细胞凋亡有抑制作用。地塞米松（0.1 μM）处理诱导INS-1细胞凋亡，这与GSK-3β活化增加和NOX 4源性ROS生成增加有关。用LiCl预处理INS-1可抑制地塞米松诱导的ROS生成和INS-1凋亡。本研究为Dex诱导胰岛β细胞凋亡提供了新的机制，为GCs诱导的糖尿病的治疗提供了新的思路。
Glucocorticoids, such as dexamethasone, are widely used anti-inflammatory drugs. Their use is frequently associated with the development of steroid- associated diabetes. Pancreatic β-cell dysfunction has been suggested to be one of the main causes of steroid-associated diabetes. However, the mechanism is not fully understood. Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase and plays an important role in energy metabolism, cell growth and apoptosis. Therefore, the contribution of GSK-3β in dexamethasone-induced pancreatic β-cell apoptosis was determined in the present study. The effect of dexamethasone treatment on rat pancreatic β-cell line (INS-1) apoptosis (determined by TUNEL and Flow Cytometry), generation of reactive oxidative stress (ROS), and the phosphorylation status of GSK-3β was determined. The inhibitory effect of GSK-3β inhibitor-lithium chloride (LiCl) on dexamethasone-induced β-cell apoptosis was also evaluated. Dexamethasone (0.1 μM) treatment induced INS-1 apoptosis, which was associated with increased GSK-3β activation and increased NOX4-derived ROS generation. Pretreatment of INS-1 with LiCl inhibited dexamethasone induced ROS generation and INS-1 apoptosis. This study provides a new mechanism of Dex induced pancreatic β cell apoptosis and may serve as a new therapeutic option for treating GCs induced diabetes.