INSULIN REGULATES TRANSCRIPTION OF THE CCAAT ENHANCER BINDING-PROTEIN(C/EBP) ALPHA-GENE, BETA-GENE, AND DELTA-GENE IN FULLY-DIFFERENTIATE 3T3-L1 ADIPOCYTES/

The effect of insulin on expression of CCAAT/enhancer binding protein (C/EBP) alpha, beta, and delta was investigated in fully-differentiate d 3T3-L1 adipocytes. Treatment of adipocytes with insulin stimulated r apid dephosphorylation of C/EBP alpha, and repressed the expression of C/EBP alpha within 2-4 h, with > 90% suppression occurring at 24 h, W hile insulin induced expression of C/EBP beta and C/EBP delta within 1 h and caused a > 20-fold increase by 4 h, expression returned to near ly pretreat ment levels by 24 h, The insulin concentration dependence of these effects was consistent with involvement of the insulin recept or, Gel shift analysis revealed that 6 h of insulin treatment decrease d the binding of nuclear C/EBP alpha while increasing binding of nucle ar C/EBP beta and C/EBP delta. The reciprocal effects of insulin on th e steady-state levels of C/EBP transcription factors can be accounted for kinetically and quantitatively by changes in their mRNA levels, wh ich can be accounted for by effects on gene transcription. The effects of insulin on adipocyte gene transcription (e.g. GLUT4) may be mediat ed, at least in part, by down-regulation of C/EBP alpha and/or its dep hosphorylation.