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Increases in Syn4 caused increases in Munc18c protein, indicating that Syn4 regulates Munc18c expression in vivo. An important finding was that female Syn4 transgenic mice exhibited an increased rate of glucose clearance during glucose tolerance tests that was repressible by the administration of tetracycline. Insulin-stimulated glucose uptake in skeletal muscle was increased by twofold in Syn4 transgenic mice compared with wild-type mice as assessed by hyperinsulinemic-euglycemic clamp analysis, consistent with a twofold increase in insulin-stimulated GLUT4 translocation in skeletal muscle. Hepatic insulin action was unaffected. Moreover, insulin content and glucose-stimulated insulin secretion by islets isolated from Syn4 transgenic mice did not differ from that of wild-type mice. In sum, these data suggest that increasing the number of Syn4-Munc18c \u201cfusion sites\u201d at the plasma membrane of skeletal muscle increases the amount of GLUT4 available to increase the overall rate of insulin-mediated glucose uptake in vivo.<\/jats:p>","DOI":"10.2337\/diabetes.53.9.2223","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"2223-2231","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":63,"title":["Syntaxin 4 Transgenic Mice Exhibit Enhanced Insulin-Mediated Glucose Uptake in Skeletal Muscle"],"prefix":"10.2337","volume":"53","author":[{"given":"Beth A.","family":"Spurlin","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Center for Diabetes Research, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela K.","family":"Nevins","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Center for Diabetes Research, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason K.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie C.","family":"Thurmond","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Center for Diabetes Research, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031209243178600_R1","doi-asserted-by":"crossref","unstructured":"Olson AL, Pessin JE: Structure, function and regulation of the mammalian facilitative glucose transporter gene family. 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