| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 23, 2006
Accepted on July 14, 2006
Division of Endocrinology, Charles R. Drew University of Medicine & Sciences, UCLA School of Medicine, Los Angeles, CA 90059 (Y.L., Y.W., N.N., A.A., T.C.F.); Department of Pediatrics, the First Hospital, JiLin University, ChangChun130021, China (C.Y); Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan (Y.N.); Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, 309 East Second Street, Pomona, CA 91766 (K.L.)
* To whom correspondence should be addressed. E-mail: dryanjunliu{at}hotmail.com.
The glucocorticoid receptor (GR) is a crucial target gene for glucocorticoid-induced insulin resistance and hepatic gluconeogenesis linked to the development of type 2 diabetes. The liver X receptors (LXRs) are nuclear receptors that play an important role in the regulation of metabolic gene linked to carbohydrate homeostasis. To assess the tissue-specific interaction of LXR with GR in the development of type 2 diabetes, we examined the possible effect of LXR agonist T0901317 on GR gene expression in vivo and in vitro in hepatocytes from db/db mice (a model of type 2 diabetes). Chronic ligand activation of LXR by a synthetic LXR T0901317 markedly decreased the expression of both GR mRNA and its protein in liver and improved the phenotype of type 2 diabetes in obese db/db mice. Suppression of hepatic GR expression was correlated with reduced levels of glucose and corresponded to the inhibition of phosphoenolpyruvate carboxykinase (PEPCK) mRNA and 11
-hydroxysteroid dehydrogenase type 1 (11-HSD1)-mediated synthesis of active corticosterone from inactive 11-dehydrocorticosterone in liver. Treatment of db/db mouse primary hepatocytes with T0901317 resulted in dramatic suppression of GR mRNA and required ongoing protein synthesis. Addition of T0901317 to primary hepatocytes also suppressed the expression of both 11-HSD1 and PEPCK. These findings suggest that some of antidiabetic actions of LXR agonist T0901317 may be mediated, at least in part, through the suppression of hepatic GR gene expression.
-HSD1 •
Glucose uptake
This article has been cited by other articles:
 |
|
 |
|
  I J Bujalska, L L Gathercole, J W Tomlinson, C Darimont, J Ermolieff, A N Fanjul, P A Rejto, and P M Stewart A novel selective 11{beta}-hydroxysteroid dehydrogenase type 1 inhibitor prevents human adipogenesis J. Endocrinol., May 1, 2008; 197(2): 297 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Roberge, A. C. Carpentier, M.-F. Langlois, J.-P. Baillargeon, J.-L. Ardilouze, P. Maheux, and N. Gallo-Payet Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1465 - E1478. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
