Interplay between H6PDH and 11β-HSD1 implicated in the pathogenesis of type 2 diabetes mellitus.
Interplay between H6PDH and 11β-HSD1 implicated in the pathogenesis of type 2 diabetes mellitus.
复制标题
DOI：
10.1016/j.bmcl.2017.07.043
复制
发表时间：
2017-09-01
影响因子：
2.7
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Yao F;Chen L;Fan Z;Teng F;Zhao Y;Guan F;Zhang M;Liu Y
11β-羟基类固醇脱氢酶1（11 β-hydroxysteroid dehydrogenase 1，11β-HSD 1）在代谢性疾病中的作用已被广泛研究。我们以前的研究报道葡萄糖可以直接调节6-磷酸己糖脱氢酶（H6 PDH）和11β-HSD 1。近年来，我们进一步研究了H6 PDH和11β-HSD 1在2型糖尿病（T2 DM）发病机制中的相互作用及其在肝硬化和胰岛素抵抗中的作用。采用T2 DM大鼠模型和转染CBRH-7919细胞的H6 PDH和11β-HSD 1 siRNA，探讨H6 PDH和11 β-HSD 1在T2 DM中的作用。结果表明，糖尿病大鼠肝脏H6 PDH和11β-HSD 1表达及活性均明显增强，PEPCK和G6 β表达及肝皮质酮水平明显升高。H6 PDH siRNA和11β-HSD 1 siRNA可相互抑制H6 PDH蛋白表达和酶活性。H6 PDH siRNA可阻断H6 PDH对胰岛素合成的促进作用，降低皮质酮诱导的胰岛素抵抗。基于这两种酶之间的相互作用，H6 PDH和11β-HPD 1可能是治疗T2 DM和代谢综合征的有效且有前景的靶点。
Extensive studies have been performed on the role of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in metabolic diseases. Our previous study reported glucose could directly regulate hexose-6-phosphate dehydrogenase (H6PDH) and 11β-HSD1. Recently, we further investigated the interplay of H6PDH and 11β-HSD1 and their roles in hepatic gluconeogenesis and insulin resistance to elucidate the importance of H6PDH and 11β-HSD1 in pathogenesis of type 2 diabetes mellitus (T2DM). T2DM rats model and H6PDH or 11β-HSD1 siRNA transfected in CBRH-7919 cells were used to explore the effect of H6PDH and 11β-HSD1 in T2DM. The results showed that the expression and activity of H6PDH and 11β-HSD1 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 11β-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 11β-HSD1 might be the effective and prospective targets for T2DM and metabolic syndromes, based on the interplay between these two enzymes.
登录
查看更多内容
影响因子：
2.7
作者：
MONDER C;LAKSHMI V
通讯作者：
LAKSHMI V
影响因子：
7.7
作者：
Liu, YJ;Nakagawa, Y;Friedman, TC
通讯作者：
Friedman, TC
影响因子：
5.8
作者：
WALKER, BR;CONNACHER, AA;EDWARDS, CRW
通讯作者：
EDWARDS, CRW
影响因子：
8.2
作者：
Alberts, P;Engblom, L;Abrahmsén, L
通讯作者：
Abrahmsén, L
影响因子：
13.8
作者：
Kadmiel M;Cidlowski JA
通讯作者：
Cidlowski JA