{"doi":"10.1210/en.2003-1523","title":"Modulation of Adipoinsular Axis in Prediabetic Zucker Diabetic Fatty Rats by Diazoxide","abstract":"AbstractDysregulation of the adipoinsular axis in male obese Zucker diabetic fatty (ZDF; fa/fa) rats, a model of type 2 diabetes, results in chronic hyperinsulinemia and increased de novo lipogenesis in islets, leading to β-cell failure and diabetes. Diazoxide (DZ; 150 mg/kg·d), an inhibitor of insulin secretion, was administered to prediabetic ZDF animals for 8 wk as a strategy for prevention of diabetes. DZ reduced food intake (P < 0.02) and rate of weight gain only in ZDF rats (P < 0.01). Plasma insulin response to glucose load was attenuated in DZ-Zucker lean rats (ZL; P < 0.01), whereas DZ-ZDF had higher insulin response to glucose than controls (P < 0.001). DZ improved hemoglobin A1c (P < 0.001) and glucose tolerance in ZDF (P < 0.001), but deteriorated hemoglobin A1c in ZL rats (P < 0.02) despite normal tolerance in the fasted state. DZ lowered plasma leptin (P < 0.001), free fatty acid, and triglyceride (P < 0.001) levels, but increased adiponectin levels (P < 0.02) only in ZDF rats. DZ enhanced β3-adrenoreceptor mRNA (P < 0.005) and adenylate cyclase activity (P < 0.01) in adipose tissue from ZDF rats only, whereas it enhanced islet β3- adrenergic receptor mRNA (P < 0.005) but paradoxically decreased islet adenylate cyclase activity (P < 0.005) in these animals. Islet fatty acid synthase mRNA (P < 0.03), acyl coenzyme A carboxylase mRNA (P < 0.01), uncoupling protein-2 mRNA (P < 0.01), and triglyceride content (P < 0.005) were only decreased in DZ-ZDF rats, whereas islet insulin mRNA and insulin content were increased in DZ-ZDF (P < 0.01) and DZ-ZL rats (P < 0.03). DZ-induced β-cell rest improved the lipid profile, enhanced the metabolic efficiency of insulin, and prevented β-cell dysfunction and diabetes in diabetes-prone animals. This therapeutic strategy may be beneficial in preventing β-cell failure and progression to diabetes in humans.","journal":"Endocrinology","year":2004,"id":15155,"datarank":2.248352008156232,"base_score":3.6888794541139363,"endowment":3.6888794541139363,"self_citation_contribution":0.5533319181170905,"citation_network_contribution":1.6950200900391412,"self_endowment_contribution":0.5533319181170905,"citer_contribution":1.6950200900391412,"corpus_percentile":null,"corpus_rank":null,"citation_count":39,"citer_count":38,"citers_with_citation_signal":35,"citers_with_endowment":35,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":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":116757,"name":"Kathryn M. Tushaus","orcid":null,"position":1,"is_corresponding":false},{"id":116756,"name":"Ramin Alemzadeh","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.6888794541139363,"endowment":3.6888794541139363,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15319354","pmcid":null,"openalex_id":"https://openalex.org/W2037631372","authors":[],"funders":[],"total_grants":0,"fwci":1.4744,"citation_percentile":0.80671045,"influential_citations":2,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":1},{"year":2014,"count":1},{"year":2015,"count":3},{"year":2016,"count":1},{"year":2017,"count":1},{"year":2018,"count":2},{"year":2020,"count":3},{"year":2021,"count":1},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2024,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://academic.oup.com/endo/article-pdf/145/12/5476/9019100/endo5476.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1210/en.2003-1523","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15319354","host_type":"repository"}],"fields_of_study":["Adipose Tissue and Metabolism","Regulation of Appetite and Obesity","Adipokines, Inflammation, and Metabolic Diseases","Medicine","Biology","Adenylyl Cyclases","Adiponectin","Adipose Tissue","Animals","Blood Glucose","Body Weight","Diabetes Mellitus, Type 2","Diazoxide","Eating","Fasting","Glucose Intolerance","Glycated Hemoglobin","Hypoglycemic Agents","Insulin","Insulin Resistance","Intercellular Signaling Peptides and Proteins","Islets of Langerhans","Leptin","Male","Obesity","RNA, Messenger","Rats","Rats, Zucker","Receptors, Adrenergic, beta-3","Triglycerides"],"mesh_terms":["Adenylyl Cyclases","Adipose Tissue","Animals","Blood Glucose","Body Weight","Diabetes Mellitus, Type 2","Diazoxide","Eating","Fasting","Glycated Hemoglobin","Hypoglycemic Agents","Insulin","Insulin Resistance","Islets of Langerhans","Male","Obesity","Rats, Zucker","RNA, Messenger","Triglycerides","Glucose Intolerance","Leptin","Receptors, Adrenergic, beta-3","Intercellular Signaling Peptides and Proteins","Rats","Adiponectin"],"keywords":["Internal medicine","Endocrinology","Hyperinsulinemia","Insulin","Lipogenesis","Diazoxide","Adiponectin","Diabetes mellitus","Medicine","Chemistry","Adipose tissue","Insulin resistance"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T16:35:55.002966Z","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":[]}