Interplay between H6PDH and 11β-HSD1 implicated in the pathogenesis of type 2 diabetes

被引：6
|
作者：
Yao, Fan [1 ]
Chen, Li [1 ,2 ]
Fan, Zheng [1 ]
Teng, Fei [1 ]
Zhao, Yali [1 ]
Guan, Fengying [1 ]
Zhang, Ming [1 ]
Liu, Yanjun [3 ]
机构：
[1] Jilin Univ, Dept Pharmacol, Coll Basic Med Sci, Changchun 130021, Peoples R China
[2] Jilin Univ, Sch Nursing, Changchun 130021, Peoples R China
[3] Univ Calif Los Angeles, Sch Med, Div Endocrinol Metab & Mol Med, Charles R Drew Univ Med & Sci, Los Angeles, CA USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 17期
基金：
中国国家自然科学基金;
关键词：
H6PDH; 11; beta-HSD1; Corticosterone; Liver; Type 2 diabetes mellitus; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; HEXOSE-6-PHOSPHATE DEHYDROGENASE; GLUCOCORTICOID-RECEPTOR; INSULIN-RESISTANCE; DB/DB MICE; EXPRESSION; CONTRIBUTE; OBESITY; HYPERGLYCEMIA; HEPATOCYTES;
D O I：
10.1016/j.bmcl.2017.07.043
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Extensive studies have been performed on the role of 11 beta-hydroxysteroid dehydrogenase 1 (11 beta-HSD1) in metabolic diseases. Our previous study reported glucose could directly regulate hexose-6-phosphate dehydrogenase (H6PDH) and 11 beta-HSD1. Recently, we further investigated the interplay of H6PDH and 11 beta-HSD1 and their roles in hepatic gluconeogenesis and insulin resistance to elucidate the importance of H6PDH and 11 beta-HSD1 in pathogenesis of type 2 diabetes mellitus (T2DM). T2DM rats model and H6PDH or 11 beta-HSD1 siRNA transfected in CBRH-7919 cells were used to explore the effect of H6PDH and 11 beta-HSD1 in T2DM. The results showed that the expression and activity of H6PDH and 11 beta-HSDI in livers of diabetic rats were increased, with the expressions of PEPCK and G6Pase or liver corticosterone increased apparently. It also showed that H6PDH siRNA and 11 beta-HSD1 siRNA could inhibit the protein expression and enzyme activity by each other. With H6PDH siRNA, the enhancement of gluconeogenesis was blocked and insulin resistance stimulated by corticosterone was reduced. H6PDH and 11 beta-HSD1 might be the effective and prospective targets for T2DM and metabolic syndromes, based on the interplay between these two enzymes. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4107 / 4113
页数：7
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