{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T19:11:29Z","timestamp":1786821089625,"version":"build-2736575974"},"reference-count":62,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,2,8]],"date-time":"2016-02-08T00:00:00Z","timestamp":1454889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG06\/008\/22062"],"award-info":[{"award-number":["RG06\/008\/22062"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>We investigated the hypothesis that elevated glucose increases contractile responses in vascular smooth muscle and that this enhanced constriction occurs due to the glucose\u2010induced PKC\u2010dependent inhibition of voltage\u2010gated potassium channels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Patch\u2010clamp electrophysiology in rat isolated mesenteric arterial myocytes was performed to investigate the glucose\u2010induced inhibition of voltage\u2010gated potassium (K<jats:sub>v<\/jats:sub>) current. To determine the effects of glucose in whole vessel, wire myography was performed in rat mesenteric, porcine coronary and human internal mammary arteries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Glucose\u2010induced inhibition of K<jats:sub>v<\/jats:sub> was PKC\u2010dependent and could be pharmacologically dissected using PKC isoenzyme\u2010specific inhibitors to reveal a PKC\u03b2\u2010dependent component of K<jats:sub>v<\/jats:sub> inhibition dominating between 0 and 10\u00a0mM glucose with an additional PKC\u03b1\u2010dependent component becoming evident at concentrations greater than 10\u00a0mM. These findings were supported using wire myography in all artery types used, where contractile responses to vessel depolarization and vasoconstrictors were enhanced by increasing bathing glucose concentration, again with evidence for distinct and complementary PKC\u03b1\/PKC\u03b2\u2010mediated components.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our results provide compelling evidence that glucose\u2010induced PKC\u03b1\/PKC\u03b2\u2010mediated inhibition of K<jats:sub>v<\/jats:sub> current in vascular smooth muscle causes an enhanced constrictor response. Inhibition of K<jats:sub>v<\/jats:sub> current causes a significant depolarization of vascular myocytes leading to marked vasoconstriction. The PKC dependence of this enhanced constrictor response may present a potential therapeutic target for improving microvascular perfusion following percutaneous coronary intervention after myocardial infarction in hyperglycaemic patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13399","type":"journal-article","created":{"date-parts":[[2015,12,10]],"date-time":"2015-12-10T02:53:53Z","timestamp":1449716033000},"page":"870-887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Distinct and complementary roles for \u03b1 and \u03b2 isoenzymes of PKC in mediating vasoconstrictor responses to acutely elevated glucose"],"prefix":"10.1111","volume":"173","author":[{"given":"Robert","family":"Jackson","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Sciences University of Leicester, Glenfield General Hospital  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Brennan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences University of Leicester, Glenfield General Hospital  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Fielding","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences University of Leicester, Glenfield General Hospital  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W","family":"Sims","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences University of Leicester, Glenfield General Hospital  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RA John","family":"Challiss","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Adlam","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences University of Leicester, Glenfield General Hospital  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain B","family":"Squire","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences University of Leicester, Glenfield General Hospital  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D","family":"Rainbow","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences University of Leicester, Glenfield General Hospital  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2003.00751.x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13348"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13349"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13354"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2004.06.001"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117724"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh0102.102359"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.2.H621"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.10.016"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000229654.45090.57"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000227514.50065.2a"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)90483-1"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1139\/o96-048"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12856"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2007.04.016"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00704.2008"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00499.2009"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.217117"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-3-19"},{"key":"e_1_2_11_21_1","first-page":"1783","article-title":"Vascular effects of acute hyperglycemia in humans are reversed by L\u2010arginine","volume":"95","author":"Giugliano D","year":"1997","journal-title":"Evidence for reduced availability of nitric oxide during hyperglycemia. Circulation"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2007.02322.x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi884"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.88.2.e14"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.02.004"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3132\/dvdr.2006.026"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1994.267.3.E369"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.11.1939"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02626-8"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1995.269.1.H348"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1540\/jsmr.44.65"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.740498"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.13.5141"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00226.2003"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh1401.093294"},{"key":"e_1_2_11_37_1","first-page":"63","article-title":"Hyperglycemia and QT interval: time for re\u2010evaluation","volume":"14","author":"Marfella R","year":"2001","journal-title":"Diabetes Nutr Metab"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1271"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199103073241002"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12955"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702481200"},{"key":"e_1_2_11_42_1","unstructured":"NICE Guidelines(2014).Type 2 diabetes: the management of type 2 diabetes. Available at: https:\/\/www.nice.org.uk\/guidance\/cg87\/resources\/guidance\u2010type\u20102\u2010diabetes\u2010pdf (October 2015)."},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.040964"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705910"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.365"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10241"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1143"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.114009"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp143"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2847"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1998.00390.x"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2006.04.009"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv029"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00894.2013"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20090322"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.12.003"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00148.2009"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1159\/000350655"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1992.263.2.H321"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00218.2011"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(02)00047-5"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1292"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1291\/hypres.31.1033"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.13399","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.13399","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.13399","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:51:44Z","timestamp":1696294304000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.13399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,8]]},"references-count":62,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1111\/bph.13399"],"URL":"https:\/\/doi.org\/10.1111\/bph.13399","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,8]]},"assertion":[{"value":"2015-06-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}