Leucine Facilitates Insulin Signaling through a G alpha(i) Protein-dependent Signaling Pathway in Hepatocytes

作者：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

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288(13): 9313-9320.

DOI：10.1074/jbc.M112.409409

• DIET-INDUCED OBESITY
• LOWERING AMINO-ACID
• SKELETAL-MUSCLE
• GLUCOSE DISPOSAL
• KINASE PLAYS
• RESISTANCE
• MTOR
• HYPERINSULINEMIA
• GLUCONEOGENESIS
• METABOLISM

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), G alpha(i) protein (pertussis toxin or siRNA against G alpha(i1) gene, or beta-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 G alpha(i1) protein-dependent manner in cultured primary hepatocytes. Together, these results show that leucine can directly facilitate insulin signaling through a G alpha(i) 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.

• 出版日期2013-3-29
• 单位华中科技大学