Isoproterenol inhibits resistin gene expression through a G(S)-protein-coupled pathway in 3T3-L1 adipocytes.
Resistin was recently identified as a hormone secreted by adipocytes which leads to insulin resistance in vivo and in vitro and might therefore be an important link between obesity and diabetes. To clarify the regulation of resistin gene expression, 3T3-L1 adipocytes were treated with various agents known to modulate insulin sensitivity, and resistin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction. Interestingly, isoproterenol treatment reduced the level of resistin mRNA to 20% of non-treated control cells. This effect was dose-dependent with significant inhibition occurring at concentrations as low as 10 nM isoproterenol. Moreover, pretreatment of adipocytes with the beta-adrenergic antagonist propranolol almost completely reversed the inhibitory effect of isoproterenol, whereas addition of the alpha-adrenergic antagonist phentolamine did not have any effect. Furthermore, the effect of isoproterenol could be mimicked by activation of G(S)-proteins and adenylyl cyclase. Thus, both cholera toxin and forskolin decreased resistin mRNA expression in a dose-dependent fashion by up to 90% of control levels. Taken together, these results suggest that resistin gene expression is regulated by a protein kinase A-dependent pathway in 3T3-L1 adipocytes.
Fasshauer
M
M
University of Leipzig, Department of Internal Medicine III, Ph.-Rosenthal-Str. 27, 04103 Leipzig, Germany.
Klein
J
J
Neumann
S
S
Eszlinger
M
M
Paschke
R
R
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D006729:Hormones, Ectopic / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D007545:Isoproterenol / Q000494:pharmacology*; D051379:Mice; D018716:Molecular Mimicry; D020932:Nerve Growth Factor; D011433:Propranolol / Q000494:pharmacology; D011506:Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D052243:Resistin; D014284:Triiodothyronine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D052243:Resistin; C499623:Retn protein, mouse; C413576:Retnla protein, mouse; D014284:Triiodothyronine; D005576:Colforsin; D003907:Dexamethasone; D002772:Cholera Toxin; D020932:Nerve Growth Factor; D011433:Propranolol; D019205:GTP-Binding Protein alpha Subunits, Gs; D007545:Isoproterenol