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

Bin Guo, Wenjian Zhang, Shiqing Xu, Jinning Lou, Shuxia Wang, Xiuli Men

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Aims 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.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalLife Sciences
Volume144
DOIs
StatePublished - Jan 1 2016

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

Keywords

  • Apoptosis
  • Dexamethasone
  • GSK-3β
  • ROS

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry, Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'GSK-3β mediates dexamethasone-induced pancreatic β cell apoptosis'. Together they form a unique fingerprint.

Cite this