{"doi":"10.2337/db23-0977","title":"Insulin Regulation of Lysine and α-Aminoadipic Acid Dynamics and Amino Metabolites in Women With and Without Insulin Resistance","abstract":"Insulin is a key regulator of amino acid metabolism. Many plasma amino acids, including lysine and its metabolite, α-aminoadipic acid (α-AA), a predictor for developing diabetes, are elevated in insulin resistance (IR). In 18 overweight women with IR and polycystic ovary syndrome compared with 12 lean control women, high physiological insulin during a euglycemic clamp failed to normalize many elevated amino acid metabolites, including branched-chain and aromatic amino acids, α-aminobutyric acid, and lysine, but normalized α-AA. To understand the underpinnings of differential responses of lysine and its metabolic product α-AA to high physiological insulin in IR compared with control participants, we developed a kinetic model using [α-15N1]-lysine and [13C1]-α-AA as tracers and measured the two tracers simultaneously in α-AA by innovative mass spectrometry. High insulin increased lysine conversion to α-AA in the IR and control groups but failed to normalize plasma lysine concentrations in IR due to a decrease in lysine metabolic clearance rate (MCR). In contrast, despite higher conversion rates of lysine to α-AA by high insulin, α-AA concentration decreased in IR because of the sustained greater MCR of α-AA. The abnormal amino acids and metabolites, even while on high physiological insulin, could potentially explain many functional derangements in IR.","journal":"Diabetes","year":2024,"id":461115,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1227679,"name":"Aneesh K Asokan","orcid":null,"position":1,"is_corresponding":false},{"id":1290070,"name":"Antigoni Z. Lalia","orcid":null,"position":2,"is_corresponding":false},{"id":1216094,"name":"Dhananjay Sakrikar","orcid":"0000-0001-8430-0120","position":3,"is_corresponding":false},{"id":399839,"name":"Ian R. Lanza","orcid":"0000-0002-9858-3384","position":4,"is_corresponding":false},{"id":335819,"name":"Xuan-Mai Petterson","orcid":null,"position":5,"is_corresponding":false},{"id":414259,"name":"K. Sreekumaran Nair","orcid":"0000-0002-0649-9469","position":6,"is_corresponding":false},{"id":479193,"name":"Alice Y. Chang","orcid":"0000-0001-7108-0499","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:04:12.271488Z","pmid":"38968429","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":[]}