Authors: C Hinault I MotheSatney N Gautier E Van Obberghen
Publish Date: 2006/03/21
Volume: 49, Issue: 5, Pages: 1017-1026
Abstract
Amino acids are well known to activate the mammalian target of the rapamycin mTOR pathway in synergy with insulin to regulate cell functions Despite recent important advances the mTOR signalling pathway is poorly understood Our previous results revealed a new pathway in which amino acids permit insulininduced activation of the protein kinase B PKB/mTOR pathway in freshly isolated adipocytes when phosphatidylinositol 3kinase PI3K is inhibited The aim of this study was to further investigate this pathway at the molecular levelWe studied the effect of amino acids on PKB phosphorylation in different cellular models or in freshly isolated adipocytes incubated in different buffers after a time course of insulin and amino acids and in the presence of pharmacological inhibitors To investigate the potential role of amino acids in insulin action the effect on glucose transport in obese rat adipocytes following a highfat diet was assessedInsulininduced PKB phosphorylation is restored by amino acids in the presence of wortmannin in adipose tissue explants and freshly isolated adipocytes but not in cultured adipocytes or hepatocytes Moreover amino acids require the presence of glucose to phosphorylate PKB and to partially rescue glucose transport in a PI3Kindependent manner The results also suggest that the amino acids act through the phosphoinositidedependent protein kinase 1 In addition amino acids were seen to improve insulinstimulated glucose transport in adipocytes from highfatfed rats
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