Increased expression of 11β-hydroxysteroid dehydrogenase type 1 in type 2 diabetic myotubes
Increased expression of 11β-hydroxysteroid dehydrogenase type 1 in type 2 diabetic myotubes
复制标题
DOI：
10.1111/j.1365-2362.2005.01552.x
复制
发表时间：
2005-10-01
影响因子：
5.5
通讯作者：
Gaster, M
中科院分区：
文献类型：
--
作者：
Abdallah, BM;Beck-Nielsen, H;Gaster, M
背景骨骼肌中糖皮质激素代谢的改变被认为是代谢综合征发病机制的一部分。循环糖皮质激素由在各种组织中通过酶11 β羟基类固醇脱氢酶（HSD）相互转化的非活性可的松和活性皮质醇组成。本研究旨在研究从健康肥胖和匹配的肥胖2型糖尿病（T2D）受试者建立的人肌管是否显示糖皮质激素受体（GR）和11 β羟类固醇脱氢酶表达水平的差异（HSD1和HSD2），研究慢性暴露于可的松是否会影响葡萄糖转运。方法在T2D和健康对照受试者的肌管中，结果T2D受试者建立的肌管显示HSD1 mRNA表达增加，但GR α、LXR α和LXR β mRNA表达无差异，而HSD2 mRNA不表达。可的松减少糖尿病肌管中的葡萄糖摄取和可的松的效果可以被废除的HSD1抑制剂carbenoxolone.Conclusions我们的研究表明，可的松减少糖尿病肌管中的葡萄糖摄取，这种效果似乎介导的mRNA HSD1表达增加强调，局部转换的非活性糖皮质激素可能是重要的胰岛素抵抗的发病机制。
Background Alterations in glucocorticoid hormone metabolism in skeletal muscle have been suggested to contribute to the pathogenesis of the metabolic syndrome. Circulating glucocorticoids consist of inactive cortisone and active cortisol interconverted in various tissues by the enzyme 11 beta hydroxysteroid dehydrogenase (HSD). This study aims to investigate whether human myotubes established from healthy obese and matched obese type 2 diabetic (T2D) subjects reveal differences in the expression level of glucocorticoid receptor (GR) and 11 beta hydroxysteroid dehydrogenase (HSD1 and HSD2), and to investigate whether chronic exposure to cortisone affects glucose transport.Methods In myotubes established from T2D and healthy control subjects we determined the mRNA expression of HSD1, HSD2, GR and determined basal and insulin-stimulated glucose uptake in myotubes precultured with cortisone, cortisol and the HSD1 inhibitor, carbenoxolone for four days.Results Myotubes established from T2D subjects showed an increased expression of HSD1 mRNA, but with no differences in mRNA of GR alpha, LXR alpha and LXR beta, whereas HSD2 mRNA was not expressed. Cortisone reduced glucose uptake in diabetic myotubes and the cortisone effect could be abolished by the HSD1 inhibitor carbenoxolone.Conclusions Our study shows that cortisone reduces glucose uptake in diabetic myotubes and that this effect seems mediated by an increased mRNA HSD1 expression emphasizing that the local conversion of inactive to active glucocorticoids may be important in the pathogenesis of insulin resistance.