{"doi":"10.1101/2023.08.10.552656","title":"Pancreatic islet α cell function and proliferation requires the arginine transporter SLC7A2","abstract":"Abstract Interrupting glucagon signaling decreases gluconeogenesis and the fractional extraction of amino acids by liver from blood resulting in lower glycemia. The resulting hyperaminoacidemia stimulates α cell proliferation and glucagon secretion via a liver-α cell axis. We hypothesized that α cells detect and respond to circulating amino acids levels via a unique amino acid transporter repertoire. We found that Slc7a2ISLC7A2 is the most highly expressed cationic amino acid transporter in α cells with its expression being three-fold greater in α than β cells in both mouse and human. Employing cell culture, zebrafish, and knockout mouse models, we found that the cationic amino acid arginine and SLC7A2 are required for α cell proliferation in response to interrupted glucagon signaling . Ex vivo and in vivo assessment of islet function in Slc7a2 −/− mice showed decreased arginine-stimulated glucagon and insulin secretion. We found that arginine activation of mTOR signaling and induction of the glutamine transporter SLC38A5 was dependent on SLC7A2, showing that both’s role in α cell proliferation is dependent on arginine transport and SLC7A2. Finally, we identified single nucleotide polymorphisms in SLC7A2 associated with HbA1c. Together, these data indicate a central role for SLC7A2 in amino acid-stimulated α cell proliferation and islet hormone secretion.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":390423,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9626,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":478909,"name":"Jade Stanley","orcid":"0000-0002-2741-8437","position":1,"is_corresponding":false},{"id":1162200,"name":"Matthew Shou","orcid":"0009-0005-8088-7581","position":2,"is_corresponding":false},{"id":430779,"name":"Linlin Yin","orcid":"0000-0002-6159-1639","position":3,"is_corresponding":false},{"id":260702,"name":"Xuan Li","orcid":"0000-0001-6319-3020","position":4,"is_corresponding":false},{"id":250522,"name":"Chunhua Dai","orcid":"0000-0002-6302-7126","position":5,"is_corresponding":false},{"id":1162201,"name":"Amber Bradley","orcid":"0000-0002-4912-371X","position":6,"is_corresponding":false},{"id":1162733,"name":"Katelyn Sellick","orcid":null,"position":7,"is_corresponding":false},{"id":310412,"name":"Greg Poffenberger","orcid":"0000-0002-7363-4683","position":8,"is_corresponding":false},{"id":250516,"name":"Katie C. Coate","orcid":"0000-0002-6604-3906","position":9,"is_corresponding":false},{"id":250518,"name":"Shristi Shrestha","orcid":"0000-0003-4519-1712","position":10,"is_corresponding":false},{"id":252943,"name":"Regina Jenkins","orcid":null,"position":11,"is_corresponding":false},{"id":63186,"name":"Kyle W. Sloop","orcid":"0000-0001-6748-9929","position":12,"is_corresponding":false},{"id":60566,"name":"Keith T. Wilson","orcid":"0000-0003-4421-1830","position":13,"is_corresponding":false},{"id":321086,"name":"Alan Attie","orcid":"0000-0002-0568-2261","position":14,"is_corresponding":false},{"id":321083,"name":"Mark P. Keller","orcid":"0000-0002-7405-5552","position":15,"is_corresponding":false},{"id":325641,"name":"Wenbiao Chen","orcid":"0000-0002-0750-8275","position":16,"is_corresponding":false},{"id":7379,"name":"Alvin C. Powers","orcid":"0000-0003-1941-5786","position":17,"is_corresponding":false},{"id":343974,"name":"E. Danielle Dean","orcid":"0000-0002-7157-5683","position":18,"is_corresponding":false},{"id":343972,"name":"Erick Spears","orcid":"0000-0003-3345-1724","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T01:18:37.743462Z","pmid":"37645716","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":[]}