{"doi":"10.1126/sciadv.abf1948","title":"GIP mediates the incretin effect and glucose tolerance by dual actions on α cells and β cells","abstract":"Glucose-dependent insulinotropic polypeptide (GIP) communicates nutrient intake from the gut to islets, enabling optimal levels of insulin secretion via the GIP receptor (GIPR) on β cells. The GIPR is also expressed in α cells, and GIP stimulates glucagon secretion; however, the role of this action in the postprandial state is unknown. Here, we demonstrate that GIP potentiates amino acid-stimulated glucagon secretion, documenting a similar nutrient-dependent action to that described in β cells. Moreover, we demonstrate that GIP activity in α cells contributes to insulin secretion by invoking paracrine α to β cell communication. Last, specific loss of GIPR activity in α cells prevents glucagon secretion in response to a meal stimulus, limiting insulin secretion and driving glucose intolerance. Together, these data uncover an important axis by which GIPR activity in α cells is necessary to coordinate the optimal level of both glucagon and insulin secretion to maintain postprandial homeostasis.","journal":"Science Advances","year":2021,"id":148492,"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":125,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"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":259348,"name":"Sarah M. Gray","orcid":"0000-0003-2370-7968","position":1,"is_corresponding":false},{"id":226895,"name":"Megan E. Capozzi","orcid":"0000-0002-7587-0663","position":2,"is_corresponding":false},{"id":632033,"name":"Emily R. Knuth","orcid":"0000-0003-1955-9253","position":3,"is_corresponding":false},{"id":632034,"name":"Enyou Jin","orcid":"0009-0005-7415-2212","position":4,"is_corresponding":false},{"id":632035,"name":"Berit Svendsen","orcid":"0000-0002-3604-000X","position":5,"is_corresponding":false},{"id":632036,"name":"Alexis L. Clifford","orcid":"0000-0001-6280-0554","position":6,"is_corresponding":false},{"id":632037,"name":"Jennifer Brown","orcid":"0000-0001-6399-4864","position":7,"is_corresponding":false},{"id":632038,"name":"Sara E. Encisco","orcid":"0000-0003-1797-9342","position":8,"is_corresponding":false},{"id":633391,"name":"Bryanna M. Chazotte","orcid":null,"position":9,"is_corresponding":false},{"id":63186,"name":"Kyle W. Sloop","orcid":"0000-0001-6748-9929","position":10,"is_corresponding":false},{"id":632039,"name":"Derek J. Nunez","orcid":"0000-0003-4704-3967","position":11,"is_corresponding":false},{"id":258194,"name":"Matthew J. Merrins","orcid":"0000-0003-1599-9227","position":12,"is_corresponding":false},{"id":226899,"name":"David A. D’Alessio","orcid":"0000-0003-4155-4870","position":13,"is_corresponding":false},{"id":226902,"name":"Jonathan E. Campbell","orcid":"0000-0003-4358-6331","position":14,"is_corresponding":false},{"id":259349,"name":"Kimberley El","orcid":"0000-0002-5550-1684","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T23:42:46.224799Z","pmid":"33712466","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":[]}