{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670319983530112.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.2337/db06-0719"}},{"identifier":{"@type":"URI","@value":"https://journals.org/diabetes/diabetes/article-pdf/56/5/1210/388237/zdb00507001210.pdf"}},{"identifier":{"@type":"URI","@value":"https://diabetesjournals.org/diabetes/article-pdf/56/5/1210/388237/zdb00507001210.pdf"}}],"dc:title":[{"@value":"Inhibiting Glycosphingolipid Synthesis Improves Glycemic Control and Insulin Sensitivity in Animal Models of Type 2 Diabetes"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Previous reports have shown that glycosphingolipids can modulate the activity of the insulin receptor, and studies in transgenic mice suggest a link between altered levels of various gangliosides and the development of insulin resistance. Here, we show that an inhibitor of glycosphingolipid synthesis can improve glucose control and increase insulin sensitivity in two different diabetic animal models. In the Zucker diabetic fatty rat, the glucosylceramide synthase inhibitor (1R,2R)-nonanoic acid[2-(2′,3′-dihydro-benzo [1, 4] dioxin-6′-yl)-2-hydroxy-1-pyrrolidin-1-ylmethyl-ethyl]- amide-l-tartaric acid salt (Genz-123346) lowered glucose and A1C levels and improved glucose tolerance. Drug treatment also prevented the loss of pancreatic β-cell function normally observed in the Zucker diabetic fatty rat and preserved the ability of the animals to secrete insulin. In the diet-induced obese mouse, treatment with Genz-123346 normalized A1C levels and improved glucose tolerance. Analysis of the phosphorylation state of the insulin receptor and downstream effectors showed increased insulin signaling in the muscles of the treated Zucker diabetic fatty rats and diet-induced obese mice. These results suggest that inhibiting glycosphingolipid synthesis can significantly improve insulin sensitivity and glucose homeostasis and may therefore represent a novel therapeutic approach for the treatment of type 2 diabetes.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383670319983530114","@type":"Researcher","foaf:name":[{"@value":"Hongmei Zhao"}],"jpcoar:affiliationName":[{"@value":"From Genzyme, Framingham, Massachusetts"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319983530119","@type":"Researcher","foaf:name":[{"@value":"Malgorzata Przybylska"}],"jpcoar:affiliationName":[{"@value":"From Genzyme, Framingham, Massachusetts"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319983530115","@type":"Researcher","foaf:name":[{"@value":"I-Huan Wu"}],"jpcoar:affiliationName":[{"@value":"From Genzyme, Framingham, Massachusetts"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319983530118","@type":"Researcher","foaf:name":[{"@value":"Jinhua Zhang"}],"jpcoar:affiliationName":[{"@value":"From Genzyme, Framingham, Massachusetts"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319983530112","@type":"Researcher","foaf:name":[{"@value":"Craig Siegel"}],"jpcoar:affiliationName":[{"@value":"From Genzyme, Framingham, Massachusetts"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319983530116","@type":"Researcher","foaf:name":[{"@value":"Svetlana Komarnitsky"}],"jpcoar:affiliationName":[{"@value":"From Genzyme, Framingham, Massachusetts"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319983530117","@type":"Researcher","foaf:name":[{"@value":"Nelson S. Yew"}],"jpcoar:affiliationName":[{"@value":"From Genzyme, Framingham, Massachusetts"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319983530113","@type":"Researcher","foaf:name":[{"@value":"Seng H. Cheng"}],"jpcoar:affiliationName":[{"@value":"From Genzyme, Framingham, Massachusetts"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00121797"},{"@type":"EISSN","@value":"1939327X"},{"@type":"PISSN","@value":"http://id.crossref.org/issn/00121797"}],"prism:publicationName":[{"@value":"Diabetes"}],"dc:publisher":[{"@value":"American Diabetes Association"}],"prism:publicationDate":"2007-05-01","prism:volume":"56","prism:number":"5","prism:startingPage":"1210","prism:endingPage":"1218"},"reviewed":"false","url":[{"@id":"https://journals.org/diabetes/diabetes/article-pdf/56/5/1210/388237/zdb00507001210.pdf"},{"@id":"https://diabetesjournals.org/diabetes/article-pdf/56/5/1210/388237/zdb00507001210.pdf"}],"createdAt":"2007-04-30","modifiedAt":"2022-11-02","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004231358522240","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Expression machinery of GM4: the excess amounts of GM3/GM4S synthase (ST3GAL5) are necessary for GM4 synthesis in mammalian cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004231358711808","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Identification of a new liver-specific c-type mRNA transcriptional variant for mouse ST3GAL5 (GM3/GM4 synthase)"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004231995364736","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"New insights on glucosylated lipids: Metabolism and functions"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004238272672384","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Ganglioside GM1 contributes to extracellular/intracellular regulation of insulin resistance, impairment of insulin signaling and down-stream eNOS activation, in human aortic endothelial cells after short- or long-term exposure to TNFα"}]},{"@id":"https://cir.nii.ac.jp/crid/1360005669361667200","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Homeostatic and pathogenic roles of\n                    <scp>GM</scp>\n                    3 ganglioside molecular species in\n                    <scp>TLR</scp>\n                    4 signaling in obesity"}]},{"@id":"https://cir.nii.ac.jp/crid/1360005744307674240","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Gangliosides Contribute to Vascular Insulin Resistance"}]},{"@id":"https://cir.nii.ac.jp/crid/1360017280656077184","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Pathophysiological Significance of GM3 Ganglioside Molecular Species With a Particular 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