{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:27:49Z","timestamp":1787927269788,"version":"build-2784847793"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Pancreatic \u03b2\u2010cell ATP\u2010sensitive potassium (K\n                      <jats:sub>ATP<\/jats:sub>\n                      ) channels play a central role in glucose homeostasis by coupling cellular metabolism to insulin secretion. Although conventional K\n                      <jats:sub>ATP<\/jats:sub>\n                      channel inhibitors are effective insulin secretagogues, their clinical use is limited by adverse effects such as hypoglycaemia. The antidepressant bupropion has been suggested to modulate K\n                      <jats:sub>ATP<\/jats:sub>\n                      channel activity; however, the underlying molecular mechanisms remain unclear. We investigated its effects on pancreatic \u03b2\u2010cell K\n                      <jats:sub>ATP<\/jats:sub>\n                      channels and molecular determinants underlying bupropion sensitivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Insulin secretion was assessed in pancreatic islets from wild\u2010type and \u03b2\u2010cell\u2010specific Kir6.2 knockout mice under basal and stimulatory glucose conditions. Electrophysiological recordings were performed in MIN6\u2010K8 and HEK293T cells expressing recombinant Kir6.2\/SUR1 channels. AlphaFold3\u2010based structural modelling was employed to predict candidate interaction regions, followed by functional analysis using SUR1 W51A.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Bupropion selectively enhanced insulin secretion at stimulatory glucose concentrations in wild\u2010type islets, but not at low glucose. This effect was abolished in \u03b2\u2010cell\u2010specific Kir6.2 knockout islets. Bupropion inhibited native K\n                      <jats:sub>ATP<\/jats:sub>\n                      currents in MIN6\u2010K8 cells (IC\n                      <jats:sub>50<\/jats:sub>\n                      \u2009=\u200914.4\u2009\u03bcM). Structural modelling suggested a potential SUR1 interaction region involving W51. The W51A mutation significantly attenuated bupropion\u2010induced inhibition without a detectable change in basal ATP\u2010free single\u2010channel activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      Bupropion inhibits pancreatic \u03b2\u2010cell K\n                      <jats:sub>ATP<\/jats:sub>\n                      channels and enhances insulin secretion in a glucose\u2010dependent manner. The SUR1\u2010TMD0 region, including residue W51, contributes to bupropion sensitivity. These findings provide mechanistic insight into the metabolic effects of bupropion and highlight the utility of AlphaFold3\u2010based structural modelling for identifying candidate interaction regions within K\n                      <jats:sub>ATP<\/jats:sub>\n                      channel complexes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70651","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:45:49Z","timestamp":1787924749000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel SUR1\u2010TMD0 interaction region contributes to glucose\u2010dependent inhibition of pancreatic K\n                    <sub>ATP<\/sub>\n                    channels by bupropion"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3711-9491","authenticated-orcid":false,"given":"Wataru","family":"Matsuoka","sequence":"first","affiliation":[{"name":"Department of Bioregulation and Pharmacological Medicine Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1340-0166","authenticated-orcid":false,"given":"Manabu","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Bioregulation and Pharmacological Medicine Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7424-4476","authenticated-orcid":false,"given":"Naoya","family":"Murao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism School of Medicine Fujita Health University  Toyoake Japan"},{"name":"Institute for Diabetes and Organoid Technology, Helmholtz Diabetes Center Helmholtz Zentrum M\u00fcnchen Deutsches Forschungszentrum f\u00fcr Gesundheit und Umwelt (GmbH)  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0554-0623","authenticated-orcid":false,"given":"Shizu","family":"Hidema","sequence":"additional","affiliation":[{"name":"Department of Bioregulation and Pharmacological Medicine Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5516-8954","authenticated-orcid":false,"given":"Ryoko","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Department of Bioregulation and Pharmacological Medicine Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5668-6994","authenticated-orcid":false,"given":"Ikuo","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Cell Science, Institute of Biomedical Sciences Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5190-6533","authenticated-orcid":false,"given":"Shoji","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Bioregulation and Pharmacological Medicine Fukushima Medical University School of Medicine  Fukushima Japan"},{"name":"DMC Institute of Life Science  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5370-5758","authenticated-orcid":false,"given":"Yuko","family":"Maejima","sequence":"additional","affiliation":[{"name":"Department of Bioregulation and Pharmacological Medicine Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1539-2532","authenticated-orcid":false,"given":"Kenju","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Department of Bioregulation and Pharmacological Medicine Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70235"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70231"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2002.86"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci25495"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.01106"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg376"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602532.2019.1620763"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1084"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23995"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46751-5"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-2166"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1143-3"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.162454"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5239.1166"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2040-1124.2010.00026.x"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.11.3065"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.32481"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/function\/zqaf002"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.028"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.31054"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2023.102541"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.24149"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2012.03.001"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04711"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci140046"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061759"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-020-0351-y"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201711978"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25074079"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00008.2017"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0079-6107(02)00053-6"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000268488.51776.53"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.4088\/pcc.v06n0403"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/wnr.0000000000002197"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-022-00683-w"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-018-0530-y"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.2337\/db24-0650"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.631960"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2112267118"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70651","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.70651","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70651","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:45:50Z","timestamp":1787924750000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70651"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":44,"alternative-id":["10.1111\/bph.70651"],"URL":"https:\/\/doi.org\/10.1111\/bph.70651","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]},"assertion":[{"value":"2026-03-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"bph.70651"}}