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 11beta 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 11beta 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 GRalpha, LXRalpha and LXRbeta, 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.
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 11beta 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 11beta 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 GRalpha, LXRalpha and LXRbeta, 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.
Authors: Margaret O Murphy; Joseph B Herald; Jacqueline Leachman; Alejandro Villasante Tezanos; Dianne M Cohn; Analia S Loria Journal: Int J Obes (Lond) Date: 2018-02-23 Impact factor: 5.095
Authors: Katherine A Hughes; Konstantinos N Manolopoulos; Javaid Iqbal; Nicholas L Cruden; Roland H Stimson; Rebecca M Reynolds; David E Newby; Ruth Andrew; Fredrik Karpe; Brian R Walker Journal: Diabetes Date: 2012-04-17 Impact factor: 9.461