Increased expression of 11beta-hydroxysteroid dehydrogenase type 1 in type 2 diabetic myotubes.
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.
Abdallah
B M
BM
KMEB, Department of Endocrinology, Odense University Hospital, Denmark.
Beck-Nielsen
H
H
Gaster
M
M
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D002229:Carbenoxolone / Q000494:pharmacology; D003348:Cortisone / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D000071518:Liver X Receptors; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000201:enzymology*; D009765:Obesity / Q000201:enzymology*; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D002229:Carbenoxolone; D003348:Cortisone; D006854:Hydrocortisone