{"doi":"10.17615/vxnk-7y39","title":"Leucine Facilitates Insulin Signaling through a Gα i 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 Akt473 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.","journal":"UNC Libraries","year":2020,"id":139901,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":604062,"name":"Sun, Xiufa","orcid":null,"position":1,"is_corresponding":false},{"id":603440,"name":"Xiang Li","orcid":"0000-0003-0724-0982","position":2,"is_corresponding":false},{"id":547859,"name":"Shuang Mei","orcid":null,"position":3,"is_corresponding":false},{"id":334284,"name":"Zhenqi Liu","orcid":"0000-0001-5077-0941","position":4,"is_corresponding":false},{"id":547432,"name":"Wenhong Cao","orcid":null,"position":5,"is_corresponding":false},{"id":603441,"name":"Xiaolei Wang","orcid":"0000-0002-6950-4309","position":6,"is_corresponding":false},{"id":566162,"name":"Xuefeng Yang","orcid":"0000-0003-3134-2065","position":7,"is_corresponding":false},{"id":603442,"name":"Liping Hao","orcid":"0000-0001-8844-0892","position":8,"is_corresponding":false},{"id":249685,"name":"Liegang Liu","orcid":"0000-0002-7029-1224","position":9,"is_corresponding":false},{"id":595934,"name":"Yan Ma","orcid":"0000-0001-6897-5064","position":10,"is_corresponding":false},{"id":547023,"name":"Haihua Gu","orcid":"0000-0003-2012-5989","position":11,"is_corresponding":false},{"id":603443,"name":"Rui Liu","orcid":"0000-0003-2610-1144","position":12,"is_corresponding":false},{"id":603439,"name":"Ping Yao","orcid":"0000-0003-0176-1971","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:13.583586Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}