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Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase

Authors
 Joshua L. Owen  ;  Yuanyuan Zhang  ;  Soo-Han Bae  ;  Midhat S. Farooqi  ;  Guosheng Liang  ;  Robert E. Hammer  ;  Joseph L. Goldstein  ;  Michael S. Browna 
Citation
 Proceedings of the National Academy of Sciences of the United States of America, Vol.109(40) : 16184-16189, 2012 
Journal Title
 Proceedings of the National Academy of Sciences of the United States of America 
ISSN
 0027-8424 
Issue Date
2012
Abstract
Insulin activates sterol regulatory element-binding protein-1c (SREBP-1c) in liver, thereby increasing fatty acid and triglyceride synthesis. We created a line of transgenic rats that produce epitope-tagged human SREBP-1c in liver under control of the constitutive apolipoprotein E promoter/enhancer. This system allows us to dissect the pathway by which insulin stimulates SREBP-1c processing without interference by the insulin-mediated increase in SREBP-1c mRNA. Rats are used because freshly isolated rat hepatocytes respond much more robustly to insulin than do mouse hepatocytes. The data reveal that insulin-mediated stimulation of SREBP-1c processing requires the mechanistic target of rapamycin complex 1 (mTORC1), which also is required for insulin-mediated SREBP-1c mRNA induction. However, in contrast to mRNA induction, insulin stimulation of SREBP-1c processing is blocked by an inhibitor of p70 S6-kinase. The data indicate that the pathways for insulin enhancement of SREBP-1c mRNA and proteolytic processing diverge after mTORC1. Stimulation of processing requires the mTORC1 target p70 S6-kinase, whereas induction of mRNA bypasses this enzyme. Insulin stimulation of both processes is blocked by glucagon. The transgenic rat system will be useful in further defining the molecular mechanism for insulin stimulation of lipid synthesis in liver in normal and diabetic states.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91750
DOI
10.1073/pnas.1213343109
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
배수한(Bae, Soo Han)
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