Insulin effects on sterol regulatory-element-binding protein-1c (SREBP-1c) transcriptional activity in rat hepatocytes

Abstract

The transcription factor sterol regulatory-element-binding protein-1c (SREBP-1c) plays a major role in the effect of insulin on the transcription of hepatic genes such as glucokinase and fatty acid synthase. We show here in cultured rat hepatocytes that insulin, through activation of the phosphatidylinositol 3-kinase pathway increases the abundance of the precursor form of SREBP-1c in endoplasmic reticulum. This precursor form is then rapidly cleaved, possibly irrespective of the continuous presence of insulin, leading to an increased content of the nuclear mature

Reciprocal regulation of the human sterol regulatory element binding protein (SREBP)‐1a promoter by Sp1 and EGR‐1 transcription factors

“…Nuclear extracts from the HEK293T cells transfected with pcDNA3‐ egr1 were prepared as previously described [8]. EMSA were performed using double‐stranded DNA oligonucleotides that were end‐labelled with [γ‐ 32 P]ATP as described in [9].…”

Review article: omega‐3 fatty acids – a promising novel therapy for non‐alcoholic fatty liver disease

“…Sterol regulatory element‐binding protein‐1 plays an important role in insulin resistance and is also a key regulator of fatty acid synthesis 47 . Levels are elevated in response to high insulin and glucose concentrations by increasing the production of its precursor 46–48 . To form mature SREBP‐1, the molecule requires to undergo two post‐translational processes – proteolytic processing and proteasomal degradation in the golgi apparatus 38 .…”

“…To form mature SREBP‐1, the molecule requires to undergo two post‐translational processes – proteolytic processing and proteasomal degradation in the golgi apparatus 38 . Following this, the mature SREBP‐1 is transported to the nucleus where, by binding to sterol regulatory elements in the promoter areas of genes, it stimulates increased de novo lipogenesis 48, 49 and glycolysis 35 . Hence, over‐expression of SREBP‐1 results in accumulation of triglycerides in the liver 50 .…”

“…Hence, over‐expression of SREBP‐1 results in accumulation of triglycerides in the liver 50 . Target genes for SREBP‐1 include glucokinase, the intracellular enzyme which is the rate limiting step for glycolysis 48 . Omega‐3s reduce the amount of mature SREBP‐1 available in the nucleus 51 and thereby inhibit the downstream stimulatory effects of insulin 35 so reducing de novo lipogenesis 52 .…”

Avaliação proteômica e lipidômica de pacientes com esteato-hepatite não alcoólica tratados com ácidos graxos ômega-3

“…A SREBP-1 é um dos reguladores-chave da síntese de ácidos graxos e desempenha um papel importante na resistência à insulina 57 . O aumento das concentrações de insulina e glicose estimulam seus precursores [57][58][59] .…”