RETRACTED: Bi-directional regulation of brown fat adipogenesis by the insulin receptor (Retracted article. See vol. 291, pg. 27434, 2016)

被引:50
作者
Entingh, AJ [1 ]
Taniguchi, CM [1 ]
Kahn, CR [1 ]
机构
[1] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Cellular & Mol Physiol, Boston, MA 02215 USA
关键词
D O I
10.1074/jbc.M303056200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Insulin is a potent inducer of adipogenesis, and differentiation of adipocytes requires many components of the insulin signaling pathway, including the insulin receptor substrate IRS-1 and phosphatidylinositol 3-kinase (PI3K). Brown pre-adipocytes in culture exhibit low levels of insulin receptor (IR), and during differentiation there is both an increase in total IR levels and a shift in the alternatively spliced forms of IR from the A isoform (-exon 11) to the B isoform (+exon 11). Brown pre-adipocyte cell lines from insulin receptor-deficient mice exhibit dramatically impaired differentiation and an inability to regulate alternative splicing of the insulin receptor. Surprisingly, re-expression of either splice isoform of IR in the IR-deficient cells fails to rescue differentiation in these cells. Likewise, overexpression of IR in control IR1ox cells also results in inhibition of differentiation and a failure to accumulate expression of the adipogenic markers peroxisome proliferator-activated receptor gamma, Glut4, and fatty acid synthase, although cells overexpressing IR retain the ability to activate PI3K and down-regulate mitogen-activated protein kinase ( MAPK) phosphorylation. Thus, differentiation of brown adipocytes requires a timed and regulated expression of IR, and either the absence or overabundance of insulin receptors in these cells dramatically inhibits differentiation.
引用
收藏
页码:33377 / 33383
页数:7
相关论文
共 35 条
[21]   TISSUE-SPECIFIC EXPRESSION OF 2 ALTERNATIVELY SPLICED INSULIN-RECEPTOR MESSENGER-RNAS IN MAN [J].
MOLLER, DE ;
YOKOTA, A ;
CARO, JF ;
FLIER, JS .
MOLECULAR ENDOCRINOLOGY, 1989, 3 (08) :1263-1269
[22]   FUNCTIONALLY DISTINCT INSULIN-RECEPTORS GENERATED BY TISSUE-SPECIFIC ALTERNATIVE SPLICING [J].
MOSTHAF, L ;
GRAKO, K ;
DULL, TJ ;
COUSSENS, L ;
ULLRICH, A ;
MCCLAIN, DA .
EMBO JOURNAL, 1990, 9 (08) :2409-2413
[23]  
RUBIN CS, 1978, J BIOL CHEM, V253, P7570
[24]   Posttranscriptional control of adipocyte differentiation through activation of phosphoinositide 3-kinase [J].
Sakaue, H ;
Ogawa, W ;
Matsumoto, M ;
Kuroda, S ;
Takata, M ;
Sugimoto, T ;
Spiegelman, BM ;
Kasuga, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (44) :28945-28952
[25]   ALTERNATIVE SPLICING OF HUMAN INSULIN-RECEPTOR MESSENGER-RNA [J].
SEINO, S ;
BELL, GI .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 159 (01) :312-316
[26]  
SELL SM, 1994, J BIOL CHEM, V269, P30769
[27]   RECEPTORS FOR INSULIN AND INSULIN-LIKE GROWTH FACTOR-I CAN FORM HYBRID DIMERS - CHARACTERIZATION OF HYBRID RECEPTORS IN TRANSFECTED CELLS [J].
SOOS, MA ;
WHITTAKER, J ;
LAMMERS, R ;
ULLRICH, A ;
SIDDLE, K .
BIOCHEMICAL JOURNAL, 1990, 270 (02) :383-390
[28]  
STEELEPERKINS G, 1988, J BIOL CHEM, V263, P11486
[29]   DIFFERENTIATION OF RAT BROWN ADIPOCYTES DURING LATE FETAL DEVELOPMENT - ROLE OF INSULIN-LIKE GROWTH-FACTOR-I [J].
TERUEL, T ;
VALVERDE, AM ;
ALVAREZ, A ;
BENITO, M ;
LORENZO, M .
BIOCHEMICAL JOURNAL, 1995, 310 :771-776
[30]   Insulin-like growth factor I and insulin induce adipogenic-related gene expression in fetal brown adipocyte primary cultures [J].
Teruel, T ;
Valverde, AM ;
Benito, M ;
Lorenzo, M .
BIOCHEMICAL JOURNAL, 1996, 319 :627-632