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Life Sci. 2016 Jan 1;144:1-7. doi: 10.1016/j.lfs.2015.11.017. Epub 2015 Nov 25.

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

Author information

1
Department of Pathophysiology, North China University of Science and Technology,Tangshan 063000, People's Republic of China.
2
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China.
3
Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA. Electronic address: swang7@uky.edu.
4
Department of Pathophysiology, North China University of Science and Technology,Tangshan 063000, People's Republic of China. Electronic address: xiulimen@126.com.

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.

KEYWORDS:

Apoptosis; Dexamethasone; GSK-3β; ROS

PMID:
26606859
PMCID:
PMC4703461
DOI:
10.1016/j.lfs.2015.11.017
[Indexed for MEDLINE]
Free PMC Article

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