{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T05:21:04Z","timestamp":1761888064765,"version":"build-2065373602"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,2,6]],"date-time":"2013-02-06T00:00:00Z","timestamp":1360108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2013,6]]},"abstract":"\n Aims<\/jats:title>\n \n G protein\u2010coupled receptor\/free fatty acid receptor 1 (\n GPR40<\/jats:styled-content>\n \/\n \n FFAR\n 1<\/jats:sub>\n <\/jats:styled-content>\n ) regulates free fatty acid\u2010induced insulin secretion. This study has been performed to clarify whether or not loss of\n GPR40<\/jats:styled-content>\n \/\n \n FFAR\n 1<\/jats:sub>\n <\/jats:styled-content>\n function exacerbates diabetes, that is, whether\n GPR40<\/jats:styled-content>\n has an essential physiological role in the development of diabetes or not.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We generated\n GPR40<\/jats:styled-content>\n \/\n \n FFAR\n 1<\/jats:sub>\n <\/jats:styled-content>\n knockout (\n KO<\/jats:styled-content>\n ) mice and analysed their phenotypes\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n under the condition of dietary or genetically induced insulin resistance.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n GPR40<\/jats:styled-content>\n \/\n \n FFAR\n 1<\/jats:sub>\n KO\n <\/jats:styled-content>\n mice kept on a high\u2010fat diet became obese, developed glucose intolerance to a similar degree as\n GPR40<\/jats:styled-content>\n \/\n \n FFAR\n 1<\/jats:sub>\n <\/jats:styled-content>\n wild\u2010type (\n WT<\/jats:styled-content>\n ) mice. In addition, the phenotype of\n KO<\/jats:styled-content>\n mice harbouring diabetogenic\n KK<\/jats:styled-content>\n background genes showed glucose intolerance at a level similar to level for control\n KK<\/jats:styled-content>\n mice. In both mouse models with insulin resistance, insulin secretion after oral glucose load and homeostasis model assessment\u2010insulin resistance (\n HOMA\u2010IR<\/jats:styled-content>\n ) did not change between\n GPR40<\/jats:styled-content>\n \/\n \n FFAR\n 1<\/jats:sub>\n KO\n <\/jats:styled-content>\n and\n WT<\/jats:styled-content>\n mice. Although glucose\u2010induced insulin secretion under high palmitate concentration was significantly lower in\n KO<\/jats:styled-content>\n than in\n WT<\/jats:styled-content>\n islets, pancreatic insulin content and insulin secretion stimulated with glucose alone were not different between\n KO<\/jats:styled-content>\n and\n WT<\/jats:styled-content>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n GPR40<\/jats:styled-content>\n \/\n \n FFAR\n 1<\/jats:sub>\n <\/jats:styled-content>\n has a major role in regulating fatty\u2010acid\u2010mediated insulin secretion, but the lack of\n GPR40<\/jats:styled-content>\n \/\n \n FFAR\n 1<\/jats:sub>\n <\/jats:styled-content>\n does not exacerbate glucose intolerance and insulin resistance induced by high\u2010fat diet or diabetogenic\n KK<\/jats:styled-content>\n gene. Our findings indicate that loss of\n GPR40<\/jats:styled-content>\n \/\n \n FFAR\n 1<\/jats:sub>\n <\/jats:styled-content>\n function does not play an important role in inducing or exacerbating diabetes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.12065","type":"journal-article","created":{"date-parts":[[2013,1,19]],"date-time":"2013-01-19T08:34:39Z","timestamp":1358584479000},"page":"538-545","source":"Crossref","is-referenced-by-count":18,"title":["Lack of\n GPR40<\/scp>\n \/\n \n FFAR\n 1<\/sub>\n <\/scp>\n does not induce diabetes even under insulin resistance condition"],"prefix":"10.1111","volume":"15","author":[{"given":"K.","family":"Matsuda\u2010Nagasumi","sequence":"first","affiliation":[{"name":"Metabolic Disease Drug Discovery Unit Takeda Pharmaceutical Company Limited Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Takami\u2010Esaki","sequence":"additional","affiliation":[{"name":"Biomolecular Research Laboratories Takeda Pharmaceutical Company Limited Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Iwachidow","sequence":"additional","affiliation":[{"name":"Biomolecular Research Laboratories Takeda Pharmaceutical Company Limited Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Yasuhara","sequence":"additional","affiliation":[{"name":"Metabolic Disease Drug Discovery Unit Takeda Pharmaceutical Company Limited Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Biomolecular Research Laboratories Takeda Pharmaceutical Company Limited Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Ogi","sequence":"additional","affiliation":[{"name":"Advanced Science Research Laboratories Takeda Pharmaceutical Company Limited Kanagawa 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