{"doi":"10.1101/2020.06.04.134866","title":"Loss of Bone Morphogenetic Protein-binding Endothelial Regulator Causes Insulin Resistance","abstract":"Accumulating evidence suggests chronic inflammation of metabolic tissues plays a causal role in obesity-induced insulin resistance. Yet, how specific endothelial factors exert impacts in metabolic tissues remains undefined. Bone morphogenetic protein (BMP)–binding endothelial regulator (BMPER) adapts endothelial cells to inflammatory stress in diverse organ microenvironments. Here we demonstrate BMPER is a driver of insulin sensitivity. Inducible knockout (iKO) of BMPER causes hyperinsulinemia, glucose intolerance and insulin resistance without increasing inflammation in metabolic tissues. Interestingly, BMPER can directly activate insulin signaling, which requires its internalization and interaction with Niemann-Pick C1 (NPC1), an integral membrane protein that transports intracellular cholesterol. These results suggest the endocrine function of the vascular endothelium maintains glucose homeostasis. Of potential clinical significance, the delivery of BMPER recombinant protein or its overexpression significantly alleviates insulin resistance and hyperglycemia in high-fat diet (HFD)-fed mice and Lepr db/db ( db/db) diabetic mice. We conclude that BMPER exhibits therapeutic potential for the treatment of diabetes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126864,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"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":574859,"name":"Luge Li","orcid":"0000-0002-4145-2607","position":1,"is_corresponding":false},{"id":575365,"name":"Qiying Fan","orcid":null,"position":2,"is_corresponding":false},{"id":574860,"name":"Aude Angelini","orcid":"0000-0001-5339-5315","position":3,"is_corresponding":false},{"id":482938,"name":"Pradip Saha","orcid":"0000-0002-8505-0917","position":4,"is_corresponding":false},{"id":513861,"name":"Huaizhu Wu","orcid":"0000-0001-6846-5531","position":5,"is_corresponding":false},{"id":233725,"name":"Christie M. Ballantyne","orcid":"0000-0002-6432-1730","position":6,"is_corresponding":false},{"id":247924,"name":"Sean M. Hartig","orcid":"0000-0002-2695-2072","position":7,"is_corresponding":false},{"id":574861,"name":"Liang Xie","orcid":"0009-0008-9851-5825","position":8,"is_corresponding":false},{"id":574862,"name":"Xinchun Pi","orcid":"0000-0002-1808-8659","position":9,"is_corresponding":false},{"id":574858,"name":"Hua Mao","orcid":"0009-0006-6068-6528","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T23:15:27.226519Z","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":[]}