{"doi":"10.1038/sj.bjp.0701628","title":"Regulation by tolbutamide and diazoxide of the electrical activity in mouse pancreatic<i>β</i>‐cells recorded<i>in vivo</i>","abstract":"<jats:p><jats:list list-type=\"explicit-label\"><jats:list-item><jats:p>The glucose‐dependence of β‐cell electrical activity and the effects of tolbutamide and diazoxide were studied in anaesthetized mice.</jats:p></jats:list-item><jats:list-item><jats:p>In untreated animals there was a direct relationship between glycaemia and the burst pattern of electrical activity. Animals with high glucose concentration showed continuous electrical activity. The application of insulin led to a steady decrease in blood glucose concentration and a transition from continuous to oscillatory activity at 7.7±0.1 m<jats:sc>M</jats:sc>glucose (mean±s.d.) and a subsequent transition from oscillatory to silent at 4.7±0.6 m<jats:sc>M</jats:sc>glucose.</jats:p></jats:list-item><jats:list-item><jats:p>At physiological blood glucose concentrations the electrical activity was oscillatory. The injection of tolbutamide (1800 mg kg<jats:sup>−1</jats:sup>) transformed this oscillatory pattern into one of continuous electrical activity. The increased electrical activity was associated with a decrease in blood glucose concentration from 7.1±0.9 (control) to 5.5±1.0 m<jats:sc>M</jats:sc>(10 min after tolbutamide injection). The effects of tolbutamide are consistent with a direct blocking effect on the K<jats:sub>ATP</jats:sub>channel that leads to membrane depolarization.</jats:p></jats:list-item><jats:list-item><jats:p>The injection of diazoxide (6000 mg kg<jats:sup>−1</jats:sup>) hyperpolarized the cells and transformed the oscillatory pattern into a silent one. This is consistent with a direct stimulant effect by diazoxide on the K<jats:sub>ATP</jats:sub>channel. The use of tolbutamide or diazoxide correspondingly led to the lengthening or shortening of the active phase of electrical activity, respectively. This indicates that<jats:italic>in vivo</jats:italic>, such activity can be modulated by the relative degree of activation or inhibition of the K<jats:sub>ATP</jats:sub>channel.</jats:p></jats:list-item><jats:list-item><jats:p>These results indicate that under physiological conditions, tolbutamide and diazoxide have direct and opposite effects on the electrical activity of pancreatic β‐cells, most likely through their action on K<jats:sub>ATP</jats:sub>channels. This is consistent with previous work carried out on<jats:italic>in vitro</jats:italic>models and explains the drugs hypo‐ and hyperglycaemic effects.</jats:p></jats:list-item></jats:list></jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic>(1998)<jats:bold>123</jats:bold>, 443–448; doi:<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038/sj.bjp.0701628\">10.1038/sj.bjp.0701628</jats:ext-link></jats:p>","journal":"British Journal of Pharmacology","year":1998,"id":46877,"datarank":1.1119738320012649,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.7057663018359333,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.7057663018359333,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":13,"citers_with_citation_signal":12,"citers_with_endowment":12,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":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":216723,"name":"Miguel Valdeolmillos","orcid":null,"position":1,"is_corresponding":false},{"id":216722,"name":"Ana Gomis","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Regulation by tolbutamide and diazoxide of the electrical activity in mouse pancreatic<i>β</i>‐cells recorded<i>in vivo</i>","abstract":"<jats:p><jats:list list-type=\"explicit-label\"><jats:list-item><jats:p>The glucose‐dependence of β‐cell electrical activity and the effects of tolbutamide and diazoxide were studied in anaesthetized mice.</jats:p></jats:list-item><jats:list-item><jats:p>In untreated animals there was a direct relationship between glycaemia and the burst pattern of electrical activity. Animals with high glucose concentration showed continuous electrical activity. The application of insulin led to a steady decrease in blood glucose concentration and a transition from continuous to oscillatory activity at 7.7±0.1 m<jats:sc>M</jats:sc>glucose (mean±s.d.) and a subsequent transition from oscillatory to silent at 4.7±0.6 m<jats:sc>M</jats:sc>glucose.</jats:p></jats:list-item><jats:list-item><jats:p>At physiological blood glucose concentrations the electrical activity was oscillatory. The injection of tolbutamide (1800 mg kg<jats:sup>−1</jats:sup>) transformed this oscillatory pattern into one of continuous electrical activity. The increased electrical activity was associated with a decrease in blood glucose concentration from 7.1±0.9 (control) to 5.5±1.0 m<jats:sc>M</jats:sc>(10 min after tolbutamide injection). The effects of tolbutamide are consistent with a direct blocking effect on the K<jats:sub>ATP</jats:sub>channel that leads to membrane depolarization.</jats:p></jats:list-item><jats:list-item><jats:p>The injection of diazoxide (6000 mg kg<jats:sup>−1</jats:sup>) hyperpolarized the cells and transformed the oscillatory pattern into a silent one. This is consistent with a direct stimulant effect by diazoxide on the K<jats:sub>ATP</jats:sub>channel. The use of tolbutamide or diazoxide correspondingly led to the lengthening or shortening of the active phase of electrical activity, respectively. This indicates that<jats:italic>in vivo</jats:italic>, such activity can be modulated by the relative degree of activation or inhibition of the K<jats:sub>ATP</jats:sub>channel.</jats:p></jats:list-item><jats:list-item><jats:p>These results indicate that under physiological conditions, tolbutamide and diazoxide have direct and opposite effects on the electrical activity of pancreatic β‐cells, most likely through their action on K<jats:sub>ATP</jats:sub>channels. This is consistent with previous work carried out on<jats:italic>in vitro</jats:italic>models and explains the drugs hypo‐ and hyperglycaemic effects.</jats:p></jats:list-item></jats:list></jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic>(1998)<jats:bold>123</jats:bold>, 443–448; doi:<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038/sj.bjp.0701628\">10.1038/sj.bjp.0701628</jats:ext-link></jats:p>","is_dataset_classified":null,"base_score":2.70805020110221,"endowment":2.70805020110221,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"9504385","pmcid":"PMC1565189","openalex_id":"https://openalex.org/W2031051368","authors":[],"funders":[],"total_grants":0,"fwci":0.2397,"citation_percentile":0.51868555,"influential_citations":2,"citation_trend":[{"year":2012,"count":1},{"year":2014,"count":1},{"year":2015,"count":1},{"year":2017,"count":1},{"year":2018,"count":1},{"year":2020,"count":2},{"year":2023,"count":1}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1038/sj.bjp.0701628","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1038/sj.bjp.0701628","host_type":"BRONZE"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1038/sj.bjp.0701628","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1038%2Fsj.bjp.0701628","host_type":"publisher"},{"url":"https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1038/sj.bjp.0701628","host_type":"publisher"},{"url":"https://doi.org/10.1038/sj.bjp.0701628","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/9504385","host_type":"repository"},{"url":"http://hdl.handle.net/10261/333514","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1565189","host_type":"repository"}],"fields_of_study":["Ion channel regulation and function","Pancreatic function and diabetes","Cardiac electrophysiology and arrhythmias","Chemistry","Medicine","Animals","Blood Glucose","Diazoxide","Dose-Response Relationship, Drug","Islets of Langerhans","Membrane Potentials","Mice","Tolbutamide"],"mesh_terms":["Animals","Blood Glucose","Diazoxide","Dose-Response Relationship, Drug","Islets of Langerhans","Membrane Potentials","Tolbutamide","Mice"],"keywords":["Diazoxide","Tolbutamide","Endocrinology","Internal medicine","Depolarization","In vivo","Chemistry","Insulin","Membrane potential","Biology","Biochemistry","Medicine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-14T21:36:13.136303Z","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":[]}