Expression of beta3-adrenoceptor and stimulation of glucose transport by beta3-agonists in brown adipocyte primary culture.
Precursor cells of brown adipocytes were isolated from the interscapular brown fat of newborn rats and cultured on collagen-coated dishes. When confluent cells were treated with dexamethasone, mRNAs for muscle/adipocyte type of glucose transporter, hormone-sensitive lipase, and CCAAT/enhancer binding protein alpha were increased remarkably, confirming a predominant effect of dexamethasone on the terminal differentiation of the cultured cells. Effects of dexamethasone on the expression of three subtypes of beta-adrenoceptor were also examined. beta1- and beta2-adrenoceptor mRNAs remained constant regardless of dexamethasone-treatment, while beta3-adrenoceptor mRNA was present only in dexamethasone-treated differentiated cells. To assess the metabolic response mediated by beta3-adrenoceptor, glucose transport into the cells was estimated. Norepinephrine enhanced glucose transport in dexamethasone-treated differentiated cells, but not in undifferentiated cells. beta3-Adrenergic agonists mimicked completely the stimulatory effect of norepinephrine at concentrations lower by two orders of magnitude. These results suggest that the beta3-adrenoceptor is expressed during the course of differentiation in brown adipocytes and plays a significant role in the response of glucose transport to adrenergic stimulation.
Nikami
H
H
Laboratory of Biochemistry, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, Sapporo.
Shimizu
Y
Y
Sumida
M
M
Minokoshi
Y
Y
Yoshida
T
T
Saito
M
M
Shimazu
T
T
D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics; D003847:Deoxyglucose / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D004983:Ethanolamines / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007527:Isoenzymes; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000235:genetics; D009124:Muscle Proteins; D009638:Norepinephrine / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D004268:DNA-Binding Proteins; D004149:Dioxoles; D004983:Ethanolamines; D051275:Glucose Transporter Type 4; D007527:Isoenzymes; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; C495694:Slc2a4 protein, rat; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C057368:BRL 37344; D003907:Dexamethasone; D003847:Deoxyglucose; D010741:Phospholipases A; D005947:Glucose; D009638:Norepinephrine