{"doi":"10.1016/j.celrep.2021.109785","title":"Serum- and glucocorticoid-induced kinase drives hepatic insulin resistance by directly inhibiting AMP-activated protein kinase","abstract":"A hallmark of type 2 diabetes (T2D) is hepatic resistance to insulin's glucose-lowering effects. The serum- and glucocorticoid-regulated family of protein kinases (SGK) is activated downstream of mechanistic target of rapamycin complex 2 (mTORC2) in response to insulin in parallel to AKT. Surprisingly, despite an identical substrate recognition motif to AKT, which drives insulin sensitivity, pathological accumulation of SGK1 drives insulin resistance. Liver-specific Sgk1 -knockout ( Sgk1 Lko ) mice display improved glucose tolerance and insulin sensitivity and are protected from hepatic steatosis when fed a high-fat diet. Sgk1 promotes insulin resistance by inactivating AMP-activated protein kinase (AMPK) via phosphorylation on inhibitory site AMPKα Ser485/491 . We demonstrate that SGK1 is dominant among SGK family kinases in regulation of insulin sensitivity, as Sgk1 , Sgk2 , and Sgk3 triple-knockout mice have similar increases in hepatic insulin sensitivity. In aggregate, these data suggest that targeting hepatic SGK1 may have therapeutic potential in T2D.","journal":"Cell Reports","year":2021,"id":160219,"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":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":672590,"name":"Yuyao Zhang","orcid":"0000-0002-8442-9693","position":1,"is_corresponding":false},{"id":672591,"name":"Sainan Li","orcid":"0000-0002-1880-6294","position":2,"is_corresponding":false},{"id":672592,"name":"Lianfeng Wu","orcid":"0000-0003-0237-2548","position":3,"is_corresponding":false},{"id":673256,"name":"Géza Fejes‐Tóth","orcid":null,"position":4,"is_corresponding":false},{"id":673257,"name":"Anikó Náray‐Fejes‐Tóth","orcid":null,"position":5,"is_corresponding":false},{"id":299215,"name":"Alexander A. Soukas","orcid":"0000-0002-9100-2436","position":6,"is_corresponding":false},{"id":672589,"name":"Ben Zhou","orcid":"0000-0001-7177-2882","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-18T23:44:43.908634Z","pmid":"34610303","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":[]}