Multiple signalling pathways mediate insulin-stimulated gene expression in 3T3-L1 adipocytes.
In differentiated 3T3-L1 adipocytes, insulin stimulated the expression of the mRNA for the genes encoding Fra-1 (>100-fold), which is a component of the AP-1 transcriptional complex, beta-actin (6.0-fold) and hexokinase II (2.4-fold). We have examined the signalling pathways involved in these effects of insulin. Rapamycin, which binds to FRAP/mTOR and completely suppressed the activation of p70S6 kinase by insulin, almost completely blocked the induction of the hexokinase II gene, and caused an approximately 50% inhibition of the induction of the Fra-1 gene. PD98059, which completely blocks MAP kinase activation by insulin, inhibited insulin-induced Fra-1 and beta-actin gene expression by approximately 70% and 40%, respectively. These findings suggest that a FRAP/mTOR-dependent pathway is responsible for the induction of hexokinase II expression, and that MAP kinase is required, at least in part, for the stimulation of beta-actin gene expression. However, the induction of Fra-1 gene expression by insulin requires both the FRAP/mTOR and MAP kinase pathways.
Culbert
Ainsley A
AA
Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
Tavaré
Jeremy M
JM
D016475:3T3 Cells; D000199:Actins / Q000235:genetics; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation; D006593:Hexokinase / Q000235:genetics; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D000099169:Fos-Related Antigen 1
D000199:Actins; D006593:Hexokinase; D007328:Insulin; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D020123:Sirolimus; D000099169:Fos-Related Antigen 1