[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-459455-105":59,"doc-detail-459455-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","transient-high-glucose-exposure-and-erk-signaling-research-letter","Transient High-Glucose Exposure and Erk Signaling - Research Letter","","Transient exposure to high D-glucose was investigated for its ability to trigger Erk2 activation and subsequent cell proliferation in human coronary artery endothelial cells (HCAEC). Cells were treated with L- or D-glucose for 1 hour followed by 23 hours in glucose-free medium. Transient high D-glucose reduced miR-138, increased Giα2 protein, inactivated Rap1, and activated Ras, culminating in Erk2 activation.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/transient-high-glucose-exposure-and-erk-signaling-research-letter/459455/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/transient-high-glucose-exposure-and-erk-signaling-research-letter/459455.png","ImageObject",300,407,{"name":92,"@type":93},"Ophelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-08","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What experimental setup was used to test transient high-glucose effects on HCAEC?","Question",{"text":112,"@type":113},"HCAEC were exposed to 183 mg/dL L-glucose or D-glucose for 1 hour, then incubated for 23 hours in a glucose-free medium.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does transient high D-glucose change Erk2-related signaling components?",{"text":117,"@type":113},"Transient high D-glucose decreases miR-138, increases Giα2 protein, inactivates Rap1, activates Ras, and thereby activates Erk2.",{"name":119,"@type":110,"acceptedAnswer":120},"What therapeutic implication is suggested by the study’s conclusion?",{"text":121,"@type":113},"Because transient high D-glucose activates Erk2 through the miRNA-138/Giα2/Rap1/Ras signaling axis, the pathway may represent a potential therapeutic target for atherosclerosis.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},459455,1790755963,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":81,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":129,"read_time":39,"preview_page_count":4},7971461741311,"https://ap-avatar.wpscdn.com/avatar/74000253aff267980c6?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779345379180704826","Circulation Reports  \nCirc Rep 2026; 8: 165–167 doi:10.1253/circrep.CR-25-0206  \nRESEARCH LETTER  \n\n| Transient High-Glucose Exposure and Erk Signaling |\n| --- |\n| Junichi Okada, MD, PhD; Tsugumichi Saito, MD, PhD;\u003Cbr>Eijiro Yamada, MD, PhD; Shuichi Okada, MD, PhD\u003Cbr>Background: Transient high-glucose exposure induces Erk2 phosphorylation and cell proliferation in human coronary artery endothelial cells (HCAEC), but the upstream mechanisms remain unclear.\u003Cbr>Methods and Results: HCAEC were exposed to 183 mg/dL L-glucose or D-glucose for 1 h followed by 23 h in a glucose-free medium. Transient high D-glucose decreased miR-138 levels, increased Giα2 protein levels, inactivated Rap1, and activated Ras, leading to Erk2 activation.\u003Cbr>Conclusions: Transient high D-glucose exposure activates Erk2 via the miRNA-138/Giα2/Rap1/Ras signaling axis, suggesting a potential therapeutic target for atherosclerosis.\u003Cbr>Key Words: Coronary artery endothelial cells; Giα2; miR-138; Ras; Rap1 |\n\nCentral Figure. Transient exposure to high D-glucose significantly decreased miR-138 levels in cultured coronary artery endothelial cells. This decreased in miR-138 levels increased Giα2 protein levels, which in turn increased Giα2 protein leading to deactivation of Rap1 . Deactivated Rap1 and activated Ras activated Erk.  \nReceived September 7, 2025; accepted September 7, 2025; J-STAGE Advance Publication released online October 25, 2025 Time for primary review: 1 day  \nDepartment of Medicine, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, NY (J.O.), USA; Department of Endocrinology and Diabetes, Gunma University Hospital, Gunma (T.S., E.Y.); and Department of Diabetes and Endocrinology, Hidaka Hospital, Gunma (S.O.), Japan  \nMailing address: Shuichi Okada, MD, PhD, Department of Diabetes and Endocrinology, Hidaka Hospital, 886 Nakao-machi,  \nTakasaki, Gunma 370-0001, [Japan. email:](Japan. email:) [okadash1823@gmail.com](okadash1823@gmail.com)  \nAll rights are reserved to the Japanese Circulation Society. For permissions, please email: [cr@j-circ.or.jp](cr@j-circ.or.jp)  \nISSN-2434-0790  \nCirculation Reports Vol.8, January 2026  \nFigure. Effect of transient exposure to high glucose on (A) Erk2 phosphorylation, (B) Ras activity, (C) Rap1 activity, (D) Giα2 protein levels and (E) miR-138 levels. Solid columns represent cells exposed to 183 mg/dL L-glucose and open columns represents cells exposed to 183 mg/dL D-glucose. All representative images are from 4 independent measurements. All data arepresented as mean ±standard deviation. Student’s t-test was used to determine statistical differences between means with P values \u003C0 .05 or \u003C0 .01 evaluated for statistical significance. (F) Proposed novel mechanism for transient high-glucose activation of Erk2 . Transient exposure to high D-glucose significantly decreased miR-138 levels in cultured coronary artery endothelial cells, which increased Giα2 protein levels, which in turn increased Giα2 protein leading to deactivation of Rap1 . Deactivated Rap1 and activated Ras activated Erk.  \nW  \ne previously reported that transient elevation of glucose levels for 1 h followed by glucose depletion increased Erk2 phosphorylation and  \ncell proliferation compared to constant glucose exposure in human coronary artery endothelial cells (HCAEC), suggesting a potential correlation of transient high-glucose exposure and atherosclerosis.1 The present study examined the mechanisms of how transient exposure of high glucose affects Erk2 activation in HCAEC.  \nWe first confirmed our previous observation1 by incubating HCAEC with either 183 mg/dL L-glucose or D-glucose for 1h followed by 23h in a glucose-free medium. Transient D-glucose exposure significantly increased Erk2 phosphorylation compared with L-glucose exposure (Figure A) . Given this activation, we next examined Ras activity and found that transient high D-glucose also activated Ras (Figure B) . Because we previously reported that Rap1 must be in","cbCaidenu2oAwGdl","https://ap.wps.com/l/cbCaidenu2oAwGdl","pdf",998121,"English","# Background\n# Methods and Results\n## Glucose exposure design\n## miR-138/Giα2/Rap1/Ras-to-Erk2 pathway\n# Conclusions\n# Figures and statistics\n# Acknowledgments / Funding / Disclosure\n# IRB Information\n# Data Availability","[{\"question\":\"What experimental setup was used to test transient high-glucose effects on HCAEC?\",\"answer\":\"HCAEC were exposed to 183 mg/dL L-glucose or D-glucose for 1 hour, then incubated for 23 hours in a glucose-free medium.\"},{\"question\":\"How does transient high D-glucose change Erk2-related signaling components?\",\"answer\":\"Transient high D-glucose decreases miR-138, increases Giα2 protein, inactivates Rap1, activates Ras, and thereby activates Erk2.\"},{\"question\":\"What therapeutic implication is suggested by the study’s conclusion?\",\"answer\":\"Because transient high D-glucose activates Erk2 through the miRNA-138/Giα2/Rap1/Ras signaling axis, the pathway may represent a potential therapeutic target for atherosclerosis.\"}]","Transient High-Glucose Exposure and Erk Signaling - Research Letter | PDF"]