{"@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/1361981468519397376.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.2337/diab.46.11.1678"}},{"identifier":{"@type":"URI","@value":"https://journals.org/diabetes/diabetes/article-pdf/46/11/1678/363708/46-11-1678.pdf"}},{"identifier":{"@type":"URI","@value":"https://diabetesjournals.org/diabetes/article-pdf/46/11/1678/363708/46-11-1678.pdf"}}],"dc:title":[{"@value":"TNF-α-Induced Insulin Resistance In Vivo and Its Prevention by Troglitazone"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Tumor necrosis factor (TNF)-α may play a role in the insulin resistance of obesity and NIDDM. Troglitazone is a new orally active hypoglycemic agent that has been shown to ameliorate insulin resistance and hyperinsu-linemia in both diabetic animal models and NIDDM subjects. To determine whether this drug could prevent the development of TNF-α-induced insulin resistance, glucose turnover was assessed in rats infused with cytokine and pretreated with troglitazone. Normal male Sprague-Dawley rats were fed normal powdered food with or without troglitazone as a food admixture (0.2%). After ∼10 days, rats were infused with TNF-a for 4–5 days, producing a plasma concentration of 632 ± 30 pg/ml. In vivo insulin action was measured by the euglycemic-hyperinsulinemic clamp technique at a sub-maximal (24 μmol · kg−1 · min−1) and maximal insulin infusion rate (240 μmol · kg−1 · min−1). TNF-α infusion resulted in a pronounced reduction in submaximal insulin-stimulated glucose disposal rate (GDR) (97 ± 10 vs. 141 ± 4 μmol · kg−1 · min−1 P &lt; 0.05), maximal GDR (175 ± 8 vs. 267 ± 6 μmol · kg−1 · min−1 P &lt; 0.01), and in insulin receptor-tyrosine kinase activity (IR-TKA) (248 ± 39 vs. 406 ± 32 pmol ATP/pmol IR, P &lt; 0.05). It also led to a marked increase in basal insulin (90 ± 24 vs. 48 ± 6 pmol/1, P &lt; 0.05) and free fatty acid (FFA) concentration (2.56 ± 0.76 vs. 0.87 ± 0.13 mmol/1, p &lt; 0.01). Troglitazone treatment completely prevented the TNF-α-induced decline in submaximal GDR (133 ± 16 vs. 141 ± 4 umol · kg−1 · min−1, NS) and maximal GDR (271 ± 19 vs. 267 ± 6 μmol · kg1 · min1, NS). The hyperlipidemia was partially corrected by troglitazone (1.53 ± 0.28 vs. 0.87 ± 0.13 mmol/1, P &lt; 0.05), while IR-TKA and insulin concentration remained unaffected by the drug. Troglitazone restores insulin action possibly by lowering the FFA concentration of the blood and/or by stimulating glucose uptake at an intracellular point distal to insulin receptor autophosphorylation in muscle. If TNF-α plays a role in the development of the obe-sity/NIDDM syndrome, troglitazone may prove useful in its treatment.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381981468519397248","@type":"Researcher","foaf:name":[{"@value":"Philip D G Miles"}],"jpcoar:affiliationName":[{"@value":"Departments of Surgery, University of California San Diego"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981468519397249","@type":"Researcher","foaf:name":[{"@value":"Oreste M Romeo"}],"jpcoar:affiliationName":[{"@value":"Departments of Surgery, University of California San Diego"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981468519397250","@type":"Researcher","foaf:name":[{"@value":"Katsuya Higo"}],"jpcoar:affiliationName":[{"@value":"Departments of Surgery, University of California San Diego"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981468519397376","@type":"Researcher","foaf:name":[{"@value":"Aaron Cohen"}],"jpcoar:affiliationName":[{"@value":"Departments of Surgery, University of California San Diego"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981468519397377","@type":"Researcher","foaf:name":[{"@value":"Karim Rafaat"}],"jpcoar:affiliationName":[{"@value":"Departments of Surgery, University of California San Diego"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981468519397378","@type":"Researcher","foaf:name":[{"@value":"Jerrold M Olefsky"}],"jpcoar:affiliationName":[{"@value":"Departments of Medicine, University of California San Diego"},{"@value":"San Diego VA Medical Center, Division of Endocrinology and Metabolism La Jolla, California"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00121797"},{"@type":"EISSN","@value":"1939327X"},{"@type":"PISSN","@value":"http://id.crossref.org/issn/00121797"},{"@type":"PISSN","@value":"https://id.crossref.org/issn/00121797"}],"prism:publicationName":[{"@value":"Diabetes"}],"dc:publisher":[{"@value":"American Diabetes Association"}],"prism:publicationDate":"1997-11-01","prism:volume":"46","prism:number":"11","prism:startingPage":"1678","prism:endingPage":"1683"},"reviewed":"false","url":[{"@id":"https://journals.org/diabetes/diabetes/article-pdf/46/11/1678/363708/46-11-1678.pdf"},{"@id":"https://diabetesjournals.org/diabetes/article-pdf/46/11/1678/363708/46-11-1678.pdf"}],"createdAt":"2013-09-19","modifiedAt":"2022-11-02","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1390001204720725248","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"The Effect of Tumor Necrosis Factor-.ALPHA. on Tissue Specificity and Selectivity to Insulin Signaling"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679219767296","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Control of oxidative stress and metabolic homeostasis by the suppression of postprandial hyperglycemia"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282681403944192","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Relationship between Serum TNF Activity and Insulin Resistance in Dairy Cows Affected with Naturally Occurring Fatty Liver."}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.2337/diab.46.11.1678"},{"@type":"CROSSREF","@value":"10.1291/hypres.26.389_references_DOI_DFfBGYhlWY8bXPOJdGdzdFGKZnq"},{"@type":"CROSSREF","@value":"10.1292/jvms.63.1021_references_DOI_DFfBGYhlWY8bXPOJdGdzdFGKZnq"},{"@type":"CROSSREF","@value":"10.2152/jmi.52.259_references_DOI_DFfBGYhlWY8bXPOJdGdzdFGKZnq"}]}