GSK-3β mediates dexamethasone-induced pancreatic β cell apoptosis

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• 作者：Bin Guo^a ; Wenjian Zhang^b ; Shiqing Xu^b ; Jinning Lou^b ; Shuxia Wang^c ; ^{swang7@uky.edu" class="auth_mail" title="E-mail the corresponding author} ; Xiuli Men^a ; ^{xiulimen@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Dexamethasone ; Apoptosis ; GSK-3β ; ROS
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 January 2016
• 年：2016
• 卷：144
• 期：Complete
• 页码：1-7
• 全文大小：1156 K

文摘

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.

Main methods

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.

Key findings

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.

Significance

This study provides a new mechanism of Dex induced pancreatic β cell apoptosis and may serve as a new therapeutic option for treating GC induced diabetes.