title: Leucine facilitates insulin signaling through a Gαi protein-dependent signaling pathway in hepatocytes.
abstract: 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.
authors: Department of Nutrition and Food Hygiene and MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. xuefengyang@gmail.com
authors: Xuefeng
authors: X
authors: Yang
authors: Shuang
authors: S
authors: Mei
authors: Xiaolei
authors: X
authors: Wang
authors: Xiang
authors: X
authors: Li
authors: Rui
authors: R
authors: Liu
authors: Yan
authors: Y
authors: Ma
authors: Liping
authors: L
authors: Hao
authors: Ping
authors: P
authors: Yao
authors: Liegang
authors: L
authors: Liu
authors: Xiufa
authors: X
authors: Sun
authors: Haihua
authors: H
authors: Gu
authors: Zhenqi
authors: Z
authors: Liu
authors: Wenhong
authors: W
authors: Cao
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D020868:Gene Silencing; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009765:Obesity / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007328:Insulin; D034741:RNA, Small Interfering; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D007930:Leucine; D005947:Glucose
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