Sema4D Deficiency Enhances Glucose Tolerance Through Acceleration of GLUT2 Synthesis in Hepatocytes

Sema4D Deficiency Enhances Glucose Tolerance Through Acceleration of GLUT2 Synthesis in Hepatocytes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Sema4D Deficiency Enhances Glucose Tolerance Through Acceleration of GLUT2 Synthesis in Hepatocytes Yanling Zhang, Xiaomei Jiang, Dongsong Wu, Hao Huang, Guiqing Jia, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4667779/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Sep, 2024 Read the published version in Journal of Translational Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract The glucose transporter 2 (GLUT2) is constitutively expressed in pancreatic beta cells and hepatocytes in mice. It is the most important receptor in glucose-stimulated insulin release and hepatic glucose transport. The Sema4D is a signaling receptor on cell membranes. The correlation between Sema4D and GLUT2 has not been reported previously. We investigated whether knockdown of Sema4D could exert a hypoglycemic effect based on the increased GLUT2 expression in Sema4D -/- mice hepatocytes. First, Sema4D -/- male mice exhibited significantly greater glucose tolerance than wild-type mice in a hyperglycemic environment. Secondly, Sema4D -/- mice had more retained GLUT2 in liver membranes after streptozotocin (STZ) injection according to an immunofluorescence assay. After STZ injection, Sema4D -/- male mice did not exhibit fasting hyperinsulinemia like wild-type mice. Finally, analysis of metabolomic and immunohistochemical data also revealed that Sema4D -/- mice produce hypoglycemic effects by enhancing the pentose phosphate pathway, but not glycogen synthesis. Thus, Sema4D may play an important role in the regulation of glucose homeostasis by affecting GLUT2 synthesis. Sema4D/CD100 GLUT2 Insulin resistance Streptozotocin Glucose tolerance Full Text Cite Share Download PDF Status: Published Journal Publication published 27 Sep, 2024 Read the published version in Journal of Translational Medicine → Version 1 posted Reviewers agreed at journal 13 Jul, 2024 Reviewers invited by journal 12 Jul, 2024 Editor assigned by journal 06 Jul, 2024 First submitted to journal 04 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4667779","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":326274453,"identity":"e890f518-01e8-4990-80fe-f65aa8706ad3","order_by":0,"name":"Yanling 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It is the most important receptor in glucose-stimulated insulin release and hepatic glucose transport. The Sema4D is a signaling receptor on cell membranes. The correlation between Sema4D and GLUT2 has not been reported previously. We investigated whether knockdown of Sema4D could exert a hypoglycemic effect based on the increased GLUT2 expression in Sema4D -/- mice hepatocytes. First, Sema4D -/- male mice exhibited significantly greater glucose tolerance than wild-type mice in a hyperglycemic environment. Secondly, Sema4D -/- mice had more retained GLUT2 in liver membranes after streptozotocin (STZ) injection according to an immunofluorescence assay. After STZ injection, Sema4D -/- male mice did not exhibit fasting hyperinsulinemia like wild-type mice. Finally, analysis of metabolomic and immunohistochemical data also revealed that Sema4D -/- mice produce hypoglycemic effects by enhancing the pentose phosphate pathway, but not glycogen synthesis. Thus, Sema4D may play an important role in the regulation of glucose homeostasis by affecting GLUT2 synthesis.\u003c/p\u003e","manuscriptTitle":"Sema4D Deficiency Enhances Glucose Tolerance Through Acceleration of GLUT2 Synthesis in Hepatocytes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-06 17:48:19","doi":"10.21203/rs.3.rs-4667779/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-07-13T22:56:40+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-12T15:48:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-06T13:14:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Translational Medicine","date":"2024-07-04T08:32:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-translational-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jtrm","sideBox":"Learn more about [Journal of Translational Medicine](http://translational-medicine.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/jtrm/default.aspx","title":"Journal of Translational Medicine","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4d826a80-739e-4dd7-accd-4af395c4e199","owner":[],"postedDate":"August 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-30T16:08:22+00:00","versionOfRecord":{"articleIdentity":"rs-4667779","link":"https://doi.org/10.1186/s12967-024-05694-7","journal":{"identity":"journal-of-translational-medicine","isVorOnly":false,"title":"Journal of Translational Medicine"},"publishedOn":"2024-09-27 15:58:18","publishedOnDateReadable":"September 27th, 2024"},"versionCreatedAt":"2024-08-06 17:48:19","video":"","vorDoi":"10.1186/s12967-024-05694-7","vorDoiUrl":"https://doi.org/10.1186/s12967-024-05694-7","workflowStages":[]},"version":"v1","identity":"rs-4667779","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4667779","identity":"rs-4667779","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}