{"doi":"10.1172/jci196357","title":"An unexpected role for the brain in the pathogenesis of diabetic ketoacidosis","abstract":"In 2011, we and others made an unexpected discovery: In rodent models of uncontrolled type 1 diabetes (T1D), the most severe manifestations of insulin deficiency -hyperglycemia and diabetic ketoacidosis (DKA) -can be fully reversed by infusing the adipocyte hormone leptin directly into the brain (1, 2).Although we were excited by this unprecedented finding, it was incompatible with the prevailing view that DKA is purely a consequence of insulin deficiency in the periphery.There was simply no context within which we could understand how an adipocyte hormone could act in the brain to accomplish such a feat.Here, we provide a modern framework for understanding how the brain, under the influence of leptin (and without the need for insulin), can reverse the most severe manifestations of uncontrolled T1D.Viewed through the lens of this new framework, our unexpected finding now seems totally predictable.Key to this understanding is the brain's role in ensuring that the body's fuel needs are met during periods of fasting.","journal":"Journal of Clinical Investigation","year":2025,"id":545783,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":315288,"name":"Gregory J. Morton","orcid":"0000-0002-8106-8386","position":1,"is_corresponding":false},{"id":231204,"name":"Irl B. Hirsch","orcid":"0000-0003-1675-8417","position":2,"is_corresponding":false},{"id":315289,"name":"Michael W. Schwartz","orcid":"0000-0003-1619-0331","position":3,"is_corresponding":false},{"id":315282,"name":"Zaman Mirzadeh","orcid":"0000-0001-5554-9744","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:53:27.751050Z","pmid":"40759579","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":[]}