{"@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/1361981470511366272.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.91.23.10878"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.91.23.10878"}},{"identifier":{"@type":"NAID","@value":"80007958559"}}],"dc:title":[{"@value":"Beta-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-beta-cell relationships."}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Hyperinsulinemia, loss of glucose-stimulated insulin secretion (GSIS), and peripheral insulin resistance coexist in non-insulin-dependent diabetes mellitus (NIDDM). Because free fatty acids (FFA) can induce these same abnormalities, we studied their role in the pathogenesis of the NIDDM of obese Zucker diabetic fatty (ZDF-drt) rats from 5 weeks of age (before the onset of hyperglycemia) until 14 weeks. Two weeks prior to hyperglycemia, plasma FFA began to rise progressively, averaging 1.9 +/- 0.06 mM at the onset of hyperglycemia (P < 0.001 vs. controls). At this time GSIS was absent and beta-cell GLUT-2 glucose transporter was decreased. The triacylglycerol content of prediabetic islets rose to 10 times that of controls and was correlated with plasma FFA (r = 0.825; P < 0.001), which, in turn, was correlated with the plasma glucose concentration (r = 0.873; P < 0.001). Reduction of hyperlipacidemia to 1.3 +/- 0.07 mM by pair feeding with lean littermates reduced all beta-cell abnormalities and prevented hyperglycemia. Normal rat islets that had been cultured for 7 days in medium containing 2 mM FFA exhibited increased basal insulin secretion at 3 mM glucose, and first-phase GSIS was reduced by 68%; in prediabetic islets, first-phase GSIS was reduced by 69% by FFA. The results suggest a role for hyperlipacidemia in the pathogenesis of NIDDM; resistance to insulin-mediated antilipolysis is invoked to explain the high FFA despite hyperinsulinemia, and sensitivity of beta cells to hyperlipacedemia is invoked to explain the FFA-induced loss of GSIS.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1580572701715394688","@type":"Researcher","foaf:name":[{"@value":"Y Lee"}],"jpcoar:affiliationName":[{"@value":"Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas 75235."}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120269565316","@type":"Researcher","foaf:name":[{"@value":"H Hirose"}],"jpcoar:affiliationName":[{"@value":"Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas 75235."}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120269565312","@type":"Researcher","foaf:name":[{"@value":"M Ohneda"}],"jpcoar:affiliationName":[{"@value":"Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas 75235."}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120269565440","@type":"Researcher","foaf:name":[{"@value":"J H Johnson"}],"jpcoar:affiliationName":[{"@value":"Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas 75235."}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120269565314","@type":"Researcher","foaf:name":[{"@value":"J D McGarry"}],"jpcoar:affiliationName":[{"@value":"Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas 75235."}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120269565315","@type":"Researcher","foaf:name":[{"@value":"R H Unger"}],"jpcoar:affiliationName":[{"@value":"Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas 75235."}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"},{"@type":"PISSN","@value":"http://id.crossref.org/issn/00278424"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"1994-11-08","prism:volume":"91","prism:number":"23","prism:startingPage":"10878","prism:endingPage":"10882"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.91.23.10878"}],"createdAt":"2006-05-31","modifiedAt":"2022-04-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050282812375138560","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@value":"インスリン抵抗性およびインスリン分泌能に関連する血中可溶性レプチン受容体および脂肪酸受容体遺伝子多型の検討"},{"@language":"ja-Kana","@value":"ガクイ ロンブン インスリン テイコウセイ オヨビ インスリン ブンピノウ ニ カンレン スル ケッチュウ カヨウセイ レプチン ジュヨウタイ オヨビ シボウサン ジュヨウタイ イデンシ タケイ ノ ケントウ"}]},{"@id":"https://cir.nii.ac.jp/crid/1050851032042948224","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@value":"肥満2型糖尿病モデル動物db/dbマウスにおけるPPARγアゴニストおよびPPARαアゴニストの影響"},{"@language":"ja-Kana","@value":"ガクイ ロンブン ヒマン 2ガタ トウニョウビョウ モデル ドウブツ db db マウス ニ オケル PPAR ガンマ アゴニスト オヨビ PPAR アルファ アゴニスト ノ エイキョウ"}]},{"@id":"https://cir.nii.ac.jp/crid/1360002219068217088","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Pancreas Fat and β Cell Mass in Humans With and Without Diabetes: An Analysis in the Japanese Population"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004232351228160","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Development of high 1-deoxynojirimycin (DNJ) content mulberry tea and use of response surface methodology to optimize tea-making 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