J Biol Chem 2013,
PMID: 23404499
Yang, Xuefeng; Mei, Shuang; Wang, Xiaolei; Li, Xiang; Liu, Rui; Ma, Yan; Hao, Liping; Yao, Ping; Liu, Liegang; Sun, Xiufa; Gu, Haihua; Liu, Zhenqi; Cao, Wenhong
In this study, we addressed the direct effect of leucine on insulin signaling. In investigating the associated mechanisms, we found that leucine itself does not activate the classical Akt- or ERK1/2 MAP kinase-dependent signaling pathways but can facilitate the insulin-induced phosphorylations of Akt(473) and ERK1/2 in a time- and dose-dependent manner in cultured hepatocytes. The leucine-facilitated insulin-induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was blocked by inhibition of c-Src (PP2), PI3K (LY294002), Gαi protein (pertussis toxin or siRNA against Gαi1 gene, or β-arrestin 2 (siRNA)). Similarly, the leucine-facilitated insulin activation of ERK1/2 was also blunted by pertussis toxin. We further show that leucine facilitated the insulin-mediated suppression of glucose production and expression of key gluconeogenic genes in a Gαi1 protein-dependent manner in cultured primary hepatocytes. Together, these results show that leucine can directly facilitate insulin signaling through a Gαi protein-dependent intracellular signaling pathway. This is the first evidence showing that macronutrients like amino acid leucine can facilitate insulin signaling through G proteins directly.
Diseases/Pathways annotated by Medline MESH: Diabetes Mellitus, Obesity
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Text Mining Data
Akt → c-Src: "
The leucine facilitated insulin induced phosphorylation of
Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was
blocked by inhibition of
c-Src ( PP2 ), PI3K ( LY294002 ), Gai protein ( pertussis toxin or siRNA against Gai1 gene, or ß-arrestin 2 ( siRNA ) )
"
Akt → insulin: "
The leucine facilitated insulin induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was blocked by inhibition of c-Src ( PP2 ), PI3K ( LY294002 ), Gai protein ( pertussis toxin or siRNA against Gai1 gene, or ß-arrestin 2 ( siRNA ) )
"
insulin → ERK1/2: "
Similarly, the leucine facilitated insulin activation of ERK1/2 was also blunted by pertussis toxin
"
Manually curated Databases
No curated data.