title: GSK-3β mediates dexamethasone-induced pancreatic β cell apoptosis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathophysiology, North China University of Science and Technology,Tangshan 063000, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Xu
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China.
authors.forename: Jinning
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA. Electronic address: swang7@uky.edu.
authors.forename: Shuxia
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, North China University of Science and Technology,Tangshan 063000, People's Republic of China. Electronic address: xiulimen@126.com.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Men
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D018021:Lithium Chloride / Q000494:pharmacology; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D017382:Reactive Oxygen Species; D003907:Dexamethasone; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride
keywords: Apoptosis; Dexamethasone; GSK-3β; ROS