Document Detail


Amino acids and leucine allow insulin activation of the PKB/mTOR pathway in normal adipocytes treated with wortmannin and in adipocytes from db/db mice.
MedLine Citation:
PMID:  15479767     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Amino acids are nutrients responsible for mammalian target of rapamycin (mTOR) regulation in mammalian cells. The mTOR protein is mainly known for its role in regulating cell growth, notably via protein synthesis. In addition to amino acids, mTOR is regulated by insulin via a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent pathway. mTOR mediates crosstalk between amino acids and insulin signaling. We show that in freshly isolated rat adipocytes, insulin stimulates the phosphorylation of mTOR on serine 2448, a protein kinase B (PKB) consensus phosphorylation site. This site is also phosphorylated by amino acids, which in contrast to insulin do not activate PKB. Moreover, insulin and amino acids have an additive effect on mTOR phosphorylation, indicating that they act via two independent pathways. Importantly, amino acids, notably leucine, permit insulin to stimulate PKB when PI 3-kinase is inhibited. They also rescue glucose transport and the mTOR pathway. Further, leucine alone can improve insulin activation of PKB in db/db mice. Our results define the importance of amino acids in insulin signaling and reveal leucine as a key amino acid in disease situations associated with insulin-resistance in adipocytes.
Authors:
Charlotte Hinault; Isabelle Mothe-Satney; Nadine Gautier; John C Lawrence; Emmanuel Van Obberghen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-10-12
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  18     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-12-03     Completed Date:  2005-05-03     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1894-6     Citation Subset:  IM    
Affiliation:
INSERM, Unité 145, Institut Fédératif de Recherche, Nice, Cédex 02, France.
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / drug effects,  enzymology*,  metabolism
Amino Acids / pharmacology*,  physiology
Androstadienes / pharmacology
Animals
Enzyme Inhibitors / pharmacology
Glucose / metabolism
Insulin / pharmacology*
Leucine / pharmacology*
Male
Mice
Mice, Mutant Strains
Phosphatidylinositol 3-Kinases / antagonists & inhibitors
Protein Kinases / metabolism*
Protein-Serine-Threonine Kinases / metabolism*
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins c-akt
Rats
Signal Transduction / drug effects
TOR Serine-Threonine Kinases
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Androstadienes; 0/Enzyme Inhibitors; 0/Insulin; 0/Proto-Oncogene Proteins; 19545-26-7/wortmannin; 50-99-7/Glucose; 61-90-5/Leucine; EC 2.7.-/Protein Kinases; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.1/mTOR protein, mouse; EC 2.7.1.1/mTOR protein, rat; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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