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| Status |
Public on Jun 30, 2010 |
| Title |
Adenosine 5’ monophosphate-activated protein kinase regulates metabolic actions of glucocorticoids by phosphorylating the glucocorticoid receptor through p38 mitogen-activated protein kinase. |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
|
| Summary |
Glucocorticoids play central roles in the regulation of energy metabolism by shifting it toward catabolism, while AMPK is the master regulator of energy homeostasis, sensing energy depletion and stimulating pathways of increasing fuel uptake and saving on peripheral supplies. We showed here that AMPK regulates glucocorticoid actions on carbohydrate metabolism by targeting the glucocorticoid receptor (GR) and modifying transcription of glucocorticoid-responsive genes in a tissue- and promoter-specific fashion. Activation of AMPK in rats reversed glucocorticoid-induced hepatic steatosis and suppressed glucocorticoid-mediated stimulation of glucose metabolism. Transcriptomic analysis in the liver suggested marked overlaps between the AMPK and glucocorticoid signaling pathways directed mostly from AMPK to glucocorticoid actions. AMPK accomplishes this by phosphorylating serine 211 of the human GR indirectly through phosphorylation and consequent activation of p38 MAPK and by altering attraction of transcriptional coregulators to DNA-bound GR. In human peripheral mononuclear cells, AMPK mRNA expression positively correlated with that of glucocorticoid-responsive GILZ, which correlated also positively with the body mass index of subjects. These results indicate that the AMPK-mediated energy control system modulates glucocorticoid action at target tissues. Since increased action of glucocorticoids is associated with development of metabolic disorders, activation of AMPK could be a promising target for developing pharmacologic interventions to these pathologies.
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| Overall design |
We tested the hypothesis by treateing rats with the synthetic glucocorticoid dexamethasone and the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR).
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| Contributor(s) |
Nader N, Ng SS, Lambrou GI, Pervanidou P, Wang Y, Chrousos GP, Kino T |
| Citation(s) |
20660302 |
| Submission date |
Jun 30, 2010 |
| Last update date |
Jul 31, 2017 |
| Contact name |
Tomoshige Kino |
| E-mail(s) |
kinot@mail.nih.gov
|
| Phone |
(301)496-6417
|
| Fax |
(301) 402-0884
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| Organization name |
National Institute of Child Health & Human Development
|
| Department |
Program in Reproductive and Adult Endocrinology
|
| Lab |
Section on Pediatric Endocrinology
|
| Street address |
10 Center Drive MSC 1109
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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| Samples (8)
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| GSM561874 |
Liver from the rats treated with vehicle for 8 hours, rep 1. |
| GSM561875 |
Liver from the rats treated with vehicle for 8 hours, rep 2. |
| GSM561876 |
Liver from the rats treated with 1.5 mg/kg animal of dexamethasone for 8 hours, rep 1. |
| GSM561877 |
Liver from the rats treated with 1.5 mg/kg animal of dexamethasone for 8 hours, rep 2. |
| GSM561878 |
Liver from the rats treated with 0.7 g/kg animal of AICAR for 8 hours, rep 1. |
| GSM561879 |
Liver from the rats treated with 0.7 g/kg animal of AICAR for 8 hours, rep 2. |
| GSM561880 |
Liver from the rats treated with 1.5 mg/kg animal of dexamethasone and 0.7 g/kg animal of AICAR for 8 hours, rep 1. |
| GSM561881 |
Liver from the rats treated with 1.5 mg/kg animal of dexamethasone and 0.7 g/kg animal of AICAR for 8 hours, rep 2. |
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| Relations |
| BioProject |
PRJNA128033 |
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