Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2013, PMID: 23404499

Leucine facilitates insulin signaling through a Gαi protein-dependent signaling pathway in hepatocytes.

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
Document information provided by NCBI PubMed

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.