{"doi":"10.1074/jbc.m110.144790","title":"Genetic Analysis of Type-1 Insulin-like Growth Factor Receptor Signaling through Insulin Receptor Substrate-1 and -2 in Pancreatic β Cells","abstract":null,"journal":"Journal of Biological Chemistry","year":2010,"id":637818,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":32372,"name":"Matthias Szabolcs","orcid":null,"position":1,"is_corresponding":false},{"id":1656305,"name":"Francesca Cinti","orcid":null,"position":2,"is_corresponding":false},{"id":1656306,"name":"Suhdir Perincheri","orcid":null,"position":3,"is_corresponding":false},{"id":104004,"name":"Domenico Accili","orcid":"0000-0002-6874-3949","position":4,"is_corresponding":false},{"id":32375,"name":"Argiris Efstratiadis","orcid":null,"position":5,"is_corresponding":false},{"id":261870,"name":"Shouhong Xuan","orcid":"0000-0003-0571-7855","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Genetic analysis of type-1 insulin-like growth factor receptor signaling through insulin receptor substrate-1 and -2 in pancreatic beta cells.","abstract":"Signaling by receptor tyrosine kinases regulates pancreatic β cell function. Inactivation of insulin receptor (InsR), IGF1 receptor (Igf1r), or Irs1 in β cells impairs insulin secretion. Conversely, Irs2 ablation impairs β cell replication. In this study, we examined aspects of the Igf1r regulatory signaling cascade in β cells. To examine genetically the involvement of Irs1 and Irs2 in Igf1r signaling, we generated double mutant mice lacking Igf1r specifically in pancreatic β cells in an Irs1- or Irs2-null background. We show that Igf1r/Irs1 double mutants do not differ phenotypically from Irs1 single mutants and exhibit hyperinsulinemia, while maintaining normal β cell mass and glucose tolerance. In contrast, lack of Igf1r function in β cells aggravates the consequences of Irs2 ablation in double mutants and results in lethal diabetes by 6 weeks of age. This additivity of phenotypic manifestations indicates that Irs2 serves a pathway that is largely independent of Igf1r signaling. Consistent with the view that the latter is the InsR pathway, we show that combined β cell-specific knock-out of both Insr and Igf1r results in a phenocopy of double mutants lacking Igf1r and Irs2. We conclude that Igf1r signals primarily through Irs1 and affects insulin secretion, whereas β cell proliferation is mainly regulated by InsR using Irs2 as a downstream signaling effector. The insulin and IGF pathways appear to control β cell functions independently and selectively.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20947509","pmcid":"PMC3003403","openalex_id":null,"authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"DK58282","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK63608","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK063608","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R37 DK058282","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK058282","title":null}],"total_grants":5,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S0021925819762711/pdf","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3003403","host_type":"repository"}],"fields_of_study":[],"mesh_terms":["Animals","Mice, Knockout","Humans","Mice","Diabetes Mellitus","Hyperinsulinism","Insulin","Receptor, IGF Type 1","Receptor, Insulin","Glucose","Signal Transduction","Cell Proliferation","Insulin-Secreting Cells","Insulin Receptor Substrate Proteins"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T19:34:57.546420Z","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":[]}