Volume 270,
Number 2,
Issue of January 13, 1995 pp. 647-654
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Insulin
Regulates Transcription of the CCAAT/Enhancer Binding Protein (C/EBP)
, 
, and 
Genes in Fully-differentiated 3T3-L1 Adipocytes
(Received for publication, August 19,
1994; and in revised form, October 17, 1994)
Ormond A.
MacDougald ,
Peter
Cornelius,
Raymond
Liu ,
M.
Daniel
Lane
The effect of insulin on expression of CCAAT/enhancer binding
protein (C/EBP) 
, 
, and 
was investigated in
fully-differentiated 3T3-L1 adipocytes. Treatment of adipocytes with
insulin stimulated rapid dephosphorylation of C/EBP, and repressed
the expression of C/EBP within 2-4 h, with >90%
suppression occurring at 24 h. While insulin induced expression of
C/EBP and C/EBP within 1 h and caused a >20-fold increase
by 4 h, expression returned to nearly pretreatment levels by 24 h. The
insulin concentration dependence of these effects was consistent with
involvement of the insulin receptor. Gel shift analysis revealed that 6
h of insulin treatment decreased the binding of nuclear C/EBP
while increasing binding of nuclear C/EBP and C/EBP. The
reciprocal effects of insulin on the steady-state levels of C/EBP
transcription factors can be accounted for kinetically and
quantitatively by changes in their mRNA levels, which can be accounted
for by effects on gene transcription. The effects of insulin on
adipocyte gene transcription (e.g. GLUT4) may be mediated, at
least in part, by down-regulation of C/EBP and/or its
dephosphorylation.
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