Alteration of 11β-Hydroxysteroid Dehydrogenase Type 1 and Glucocorticoid Receptor by Ethanol in Rat Liver and Mouse Hepatoma Cells. (30th May 2013)

• Record Type: Journal Article
• Authors: Meng, Zhaojie; Bao, Xueying; Zhang, Ming; Wei, Shengnan; Chang, Wenguang; Li, Jing; Chen, Li; Nyomba, B. L. Grégoire
• Other Names: Li Ji Academic Editor.
• Is Part Of: Journal of diabetes research. Volume 2013(2013)
• Publication Date: 2013-05-30
• Subjects: Diabetes -- Periodicals; Diabetes -- Pathophysiology -- Periodicals; Diabetes -- Prevention -- Periodicals; Diabetes -- Etiology -- Periodicals; Diabetes -- Epidemiology -- Periodicals; Diabetes -- Pathogenesis -- Periodicals; 616.462005
• DOI: 10.1155/2013/218102
• Languages: English
• ISSNs: 2314-6745

Abstract

Abstract : Alcohol is a potential risk factor of type 2 diabetes, but its underlying mechanism is unclear. To explore this issue, Wistar rats and mouse hepatoma cells (Hepa 1–6) were exposed to ethanol, 8 g·kg −1 ·d −1 for 3 months and 100 mM for 48 h, respectively. Glucose and insulin tolerance tests in vivo were performed, and protein levels of 11β -hydroxysteroid dehydrogenase type 1 (11β -HSD1) and glucocorticoid receptor (GR) in liver and Hepa 1–6 cells were measured. Alterations of key enzymes of gluconeogenesis phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6Pase), as well as glycogen synthase kinase 3a (GSK3 α ), were also examined. The results revealed that glucose levels were increased, and insulin sensitivity was impaired accompanied with liver injury in rats exposed to ethanol compared with controls. The 11β -HSD1, GR, PEPCK, G6Pase, and GSK3 α proteins were increased in the liver of rats treated with ethanol compared with controls. Ethanol-exposed Hepa 1–6 cells also showed higher expression of 11β -HSD1, GR, PEPCK, G6Pase, and GSK3 α proteins than control cells. After treatment of Hepa 1–6 cells exposed to ethanol with the GR inhibitor RU486, the expression of 11β -HSD1 and GR was significantly decreased. At the same time the increases in PEPCK, G6Pase, and GSK3 α levels induced by ethanol in Hepa 1–6 cells were also attenuated by RU486. The results indicate that ethanol causes glucose intolerance by increasing hepatic expression of 11β -HSD1 and GR, which leads to increased expression of gluconeogenic and glycogenolytic enzymes.