{"doi":"10.1101/2020.12.24.424313","title":"Role of hypothalamic MAPK/ERK signaling in diabetes remission induced by the central action of fibroblast growth factor 1","abstract":"Summary The capacity of the brain to elicit sustained remission of hyperglycemia in rodent models of type 2 diabetes following intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) is well established. Here, we show that following icv FGF1 injection, hypothalamic signaling by extracellular signal-regulated kinases 1 and 2 (ERK1/2), members of the mitogen-activated protein kinase (MAPK) family is induced for at least 24h. Further, we show that in diabetic Lep ob/ob mice, this prolonged response is required for the sustained antidiabetic action of FGF1, since it is abolished by sustained (but not acute) pharmacologic blockade of hypothalamic MAPK/ERK signaling. We also demonstrate that FGF1 R50E, a FGF1 mutant that activates FGF receptors but induces only transient hypothalamic MAPK/ERK signaling, fails to mimic the sustained glucose lowering induced by FGF1. These data identify sustained activation of hypothalamic MAPK/ERK signaling as playing an essential role in the mechanism underlying diabetes remission induced by icv FGF1 administration.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":132014,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9608,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":315287,"name":"Marie A. Bentsen","orcid":"0000-0002-2561-2308","position":1,"is_corresponding":false},{"id":43277,"name":"Dylan M. Rausch","orcid":"0000-0001-6095-4891","position":2,"is_corresponding":false},{"id":322179,"name":"Bao Anh Phan","orcid":null,"position":3,"is_corresponding":false},{"id":587463,"name":"Danielle Wieck","orcid":null,"position":4,"is_corresponding":false},{"id":587464,"name":"Huzaifa Wasanwala","orcid":null,"position":5,"is_corresponding":false},{"id":587465,"name":"Miles E. Matsen","orcid":null,"position":6,"is_corresponding":false},{"id":587466,"name":"Nikhil Acharya","orcid":null,"position":7,"is_corresponding":false},{"id":563230,"name":"Nicole E. Richardson","orcid":"0000-0002-2772-3060","position":8,"is_corresponding":false},{"id":305657,"name":"Xin Zhao","orcid":"0000-0001-8502-0139","position":9,"is_corresponding":false},{"id":586937,"name":"Peng Zhai","orcid":"0009-0002-0809-0111","position":10,"is_corresponding":false},{"id":347782,"name":"Anna Secher","orcid":"0000-0002-6276-5389","position":11,"is_corresponding":false},{"id":315288,"name":"Gregory J. Morton","orcid":"0000-0002-8106-8386","position":12,"is_corresponding":false},{"id":21666,"name":"Tune H. Pers","orcid":"0000-0003-0207-4831","position":13,"is_corresponding":false},{"id":315289,"name":"Michael W. Schwartz","orcid":"0000-0003-1619-0331","position":14,"is_corresponding":false},{"id":315283,"name":"Jarrad M. Scarlett","orcid":"0000-0003-1019-346X","position":15,"is_corresponding":false},{"id":315284,"name":"Jenny M. Brown","orcid":"0000-0002-5072-4491","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T23:16:07.542484Z","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":[]}