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AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes : a novel mechanism in Cushing's syndrome

Christ-Crain, M. and Kola, B. and Lolli, F. and Fekete, C. and Seboek, D. and Wittmann, G. and Feltrin, D. and Igreja, S. C. and Ajodha, S. and Harvey-White, J. and Kunos, G. and Müller, B. and Pralong, F. and Aubert, G. and Arnaldi, G. and Giacchetti, G. and Boscaro, M. and Grossman, A. B. and Korbonits, M.. (2008) AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes : a novel mechanism in Cushing's syndrome. FASEB Journal, 22 (6). pp. 1672-1683.

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Official URL: http://edoc.unibas.ch/dok/A6006614

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Abstract

Chronic exposure to glucocorticoid hormones, resulting from either drug treatment or Cushing's syndrome, results in insulin resistance, central obesity, and symptoms similar to the metabolic syndrome. We hypothesized that the major metabolic effects of corticosteroids are mediated by changes in the key metabolic enzyme adenosine monophosphate-activated protein kinase (AMPK) activity. Activation of AMPK is known to stimulate appetite in the hypothalamus and stimulate catabolic processes in the periphery. We assessed AMPK activity and the expression of several metabolic enzymes in the hypothalamus, liver, adipose tissue, and heart of a rat glucocorticoid-excess model as well as in in vitro studies using primary human adipose and primary rat hypothalamic cell cultures, and a human hepatoma cell line treated with dexamethasone and metformin. Glucocorticoid treatment inhibited AMPK activity in rat adipose tissue and heart, while stimulating it in the liver and hypothalamus. Similar data were observed in vitro in the primary adipose and hypothalamic cells and in the liver cell line. Metformin, a known AMPK regulator, prevented the corticosteroid-induced effects on AMPK in human adipocytes and rat hypothalamic neurons. Our data suggest that glucocorticoid-induced changes in AMPK constitute a novel mechanism that could explain the increase in appetite, the deposition of lipids in visceral adipose and hepatic tissue, as well as the cardiac changes that are all characteristic of glucocorticoid excess. Our data suggest that metformin treatment could be effective in preventing the metabolic complications of chronic glucocorticoid excess.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Allgemeine innere Medizin AG > Argovia Professur für Medizin (Müller)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Allgemeine innere Medizin AG > Argovia Professur für Medizin (Müller)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie > Endokrinologie (Christ-Crain)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie > Endokrinologie (Christ-Crain)
UniBasel Contributors:Müller, Beat and Christ-Crain, Mirjam
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Federation of American Society of Experimental Biology
ISSN:0892-6638
e-ISSN:1530-6860
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:28 Nov 2017 11:07
Deposited On:08 Nov 2012 16:16

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