Posttranslational processing of SREBP-1 in rat hepatocytes is regulated by insulin and cAMP.
Insulin and cAMP have opposing effects on de novo fatty acid synthesis in liver and in cultured hepatocytes mediated by sterol-regulatory element binding protein (SREBP). To determine whether these agents regulate the cleavage of full-length SREBP to generate the transcriptionally active N-terminal fragment (nSREBP) in primary rat hepatocytes, an adenoviral vector (Ad-SREBP-1a) was constructed to constitutively express full-length SREBP-1a. Insulin increased, and dibutyryl (db)-cAMP inhibited, generation of nSREBP-1a from its full-length precursor. Insulin stimulated processing of SREBP-1a within 1h, and the effect was sustained for at least 24h. The initial stimulation of SREBP processing by insulin preceded measurable reduction in Insig-2 mRNA levels. Rat hepatocytes were also infected with an adenovirus expressing the nuclear form of SREBP-1c (Ad-nSREBP-1c). Insulin increased the half-life of constitutively expressed nSREBP-1c, and this effect of insulin was also inhibited by db-cAMP.
Yellaturu
Chandrahasa R
CR
Department of Veterans Affairs Medical Center, Memphis, TN, USA.
Deng
Xiong
X
Cagen
Lauren M
LM
Wilcox
Henry G
HG
Park
Edwards A
EA
Raghow
Rajendra
R
Elam
Marshall B
MB
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C467727:INSIG2 protein, human; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D000242:Cyclic AMP