{"doi":"10.2337/db20-0192","title":"Induction of Core Circadian Clock Transcription Factor Bmal1 Enhances β-Cell Function and Protects Against Obesity-Induced Glucose Intolerance","abstract":"Type 2 diabetes mellitus (T2DM) is characterized by β-cell dysfunction as a result of impaired glucose-stimulated insulin secretion (GSIS). Studies show that β-cell circadian clocks are important regulators of GSIS and glucose homeostasis. These observations raise the question about whether enhancement of the circadian clock in β-cells will confer protection against β-cell dysfunction under diabetogenic conditions. To test this, we used an approach by first generating mice with β-cell–specific inducible overexpression of Bmal1 (core circadian transcription factor; β-Bmal1OV). We subsequently examined the effects of β-Bmal1OV on the circadian clock, GSIS, islet transcriptome, and glucose metabolism in the context of diet-induced obesity. We also tested the effects of circadian clock–enhancing small-molecule nobiletin on GSIS in mouse and human control and T2DM islets. We report that β-Bmal1OV mice display enhanced islet circadian clock amplitude and augmented in vivo and in vitro GSIS and are protected against obesity-induced glucose intolerance. These effects were associated with increased expression of purported BMAL1-target genes mediating insulin secretion, processing, and lipid metabolism. Furthermore, exposure of isolated islets to nobiletin enhanced β-cell secretory function in a Bmal1-dependent manner. This work suggests therapeutic targeting of the circadian system as a potential strategy to counteract β-cell failure under diabetogenic conditions.","journal":"Diabetes","year":2020,"id":60462,"datarank":1.8638934748578397,"base_score":4.143134726391533,"endowment":4.143134726391533,"self_citation_contribution":0.62147020895873,"citation_network_contribution":1.2424232658991097,"self_endowment_contribution":0.62147020895873,"citer_contribution":1.2424232658991097,"corpus_percentile":null,"corpus_rank":null,"citation_count":62,"citer_count":59,"citers_with_citation_signal":48,"citers_with_endowment":48,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9415,"is_data_producer":true,"deposit_databanks":{"figshare":["10.2337/figshare.13103045"]},"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":241936,"name":"Aleksey V. Matveyenko","orcid":"0000-0001-7761-4842","position":1,"is_corresponding":false},{"id":265609,"name":"Kuntol Rakshit","orcid":null,"position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T21:08:47.852401Z","pmid":"33087455","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":[]}