Beta-adrenoceptors, but not alpha-adrenoceptors, stimulate AMP-activated protein kinase in brown adipocytes independently of uncoupling protein-1.
Diabetologia
; 48(11): 2386-95, 2005 Nov.
Article
em En
| MEDLINE
| ID: mdl-16160864
ABSTRACT
AIMS/HYPOTHESIS:
Brown adipocytes provide a potentially important model system for understanding AMP-activated protein kinase (AMPK) regulation, where adrenergic stimulation leads to mitochondrial uncoupling through uncoupling protein-1 (UCP1) activity. AMPK is a sensor of energy homeostasis and has been implicated in glucose and lipid metabolism in several insulin-sensitive tissues. The aim of this study was to characterise the potential role of AMPK in adrenergically mediated glucose uptake and to find out whether UCP1 is involved in the adrenergic activation of AMPK.METHODS:
We used primary brown adipocytes differentiated in culture and measured AMPK phosphorylation and glucose uptake following adrenergic activation.RESULTS:
Treatment of adipocytes with noradrenaline (norepinephrine) caused phosphorylation of AMPK via beta-adrenoceptors and not alpha(1)- or alpha(2)-adrenoceptors. This effect was not beta(3)-adrenoceptor specific, since responses remained intact in adipocytes from beta(3)-adrenoceptor knock-out mice. These effects were also mimicked by forskolin and cAMP analogues. Treatment of cells with adenine 8-beta-D-arabinofuranoside, an AMPK inhibitor, partially blocked beta-adrenoceptor-mediated increases in glucose uptake. Brown adipocytes are characterised by the production of UCP1, which can uncouple the mitochondria. Using adipocytes from Ucp1(+/+) and Ucp1(-/-) mice, we showed that noradrenaline-mediated phosphorylation of AMPK does not require the presence or activity of UCP1. CONCLUSIONS/INTERPRETATION:
These results suggest a pathway where increases in cAMP mediated by beta-adrenoceptors leads to activation of AMPK in brown adipocytes, which contributes in part to beta-adrenoceptor-mediated increases in glucose uptake, an effect independent of the presence or function of UCP1.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tecido Adiposo Marrom
/
Proteínas de Transporte
/
Receptores Adrenérgicos alfa
/
Receptores Adrenérgicos beta
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Proteínas Serina-Treonina Quinases
/
Adipócitos
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Proteínas de Membrana
/
Complexos Multienzimáticos
Idioma:
En
Revista:
Diabetologia
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Suécia