{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:40:41Z","timestamp":1791268841324,"version":"4.1.0"},"reference-count":31,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2013,9]]},"DOI":"10.1124\/jpet.113.206466","type":"journal-article","created":{"date-parts":[[2013,7,13]],"date-time":"2013-07-13T00:17:43Z","timestamp":1373674663000},"page":"443-452","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":25,"title":["Chronic Treatment with Novel GPR40 Agonists Improve Whole-Body Glucose Metabolism Based on the Glucose-Dependent Insulin Secretion"],"prefix":"10.1016","volume":"346","author":[{"given":"Hirotsugu","family":"Tanaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Oshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Minoura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Negoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Sakuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiyoshi","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Matsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Shibasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/jpet.113.206466_bib1","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/S0140-6736(98)07037-8","article-title":"Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)","volume":"352","year":"1998","journal-title":"Lancet"},{"key":"10.1124\/jpet.113.206466_bib2","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1463-1326.2011.01525.x","article-title":"GPR40-induced insulin secretion by the novel agonist TAK-875: first clinical findings in patients with type 2 diabetes","volume":"14","author":"Araki","year":"2012","journal-title":"Diabetes Obes Metab"},{"issue":"Suppl. 2","key":"10.1124\/jpet.113.206466_bib3","first-page":"S59","article-title":"Liraglutide: a review of the first once-daily GLP-1 receptor agonist","volume":"17","author":"Bode","year":"2011","journal-title":"Am J Manag Care"},{"key":"10.1124\/jpet.113.206466_bib4","doi-asserted-by":"crossref","first-page":"11303","DOI":"10.1074\/jbc.M211495200","article-title":"The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids","volume":"278","author":"Briscoe","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1124\/jpet.113.206466_bib5","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/S0140-6736(11)61879-5","article-title":"TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial","volume":"379","author":"Burant","year":"2012","journal-title":"Lancet"},{"key":"10.1124\/jpet.113.206466_bib6","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/S0149-2918(96)80017-8","article-title":"Metformin: a new oral biguanide","volume":"18","author":"Campbell","year":"1996","journal-title":"Clin Ther"},{"key":"10.1124\/jpet.113.206466_bib7","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1007\/s00125-013-2905-1","volume":"56","author":"Charbonnel","year":"2013","journal-title":"Diabetologia"},{"key":"10.1124\/jpet.113.206466_bib8","doi-asserted-by":"crossref","first-page":"7061","DOI":"10.1021\/jm8010178","article-title":"Discovery of potent and selective agonists for the free fatty acid receptor 1 (FFA(1)\/GPR40), a potential target for the treatment of type II diabetes","volume":"51","author":"Christiansen","year":"2008","journal-title":"J Med Chem"},{"key":"10.1124\/jpet.113.206466_bib9","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1111\/j.1742-1241.2010.02382.x","article-title":"Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis","volume":"64","author":"Engel","year":"2010","journal-title":"Int J Clin Pract"},{"key":"10.1124\/jpet.113.206466_bib10","doi-asserted-by":"crossref","first-page":"E670","DOI":"10.1152\/ajpendo.00035.2005","article-title":"Oleic acid interacts with GPR40 to induce Ca2+ signaling in rat islet beta-cells: mediation by PLC and L-type Ca2+ channel and link to insulin release","volume":"289","author":"Fujiwara","year":"2005","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"10.1124\/jpet.113.206466_bib11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.numecd.2005.12.003","article-title":"A one-year study comparing the efficacy and safety of rosiglitazone and glibenclamide in the treatment of type 2 diabetes","volume":"17","author":"Hanefeld","year":"2007","journal-title":"Nutr Metab Cardiovasc Dis"},{"issue":"Suppl 2","key":"10.1124\/jpet.113.206466_bib12","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1002\/dmrr.249","article-title":"The mode of action of thiazolidinediones","volume":"18","author":"Hauner","year":"2002","journal-title":"Diabetes Metab Res Rev"},{"key":"10.1124\/jpet.113.206466_bib13","doi-asserted-by":"crossref","first-page":"4612","DOI":"10.1210\/jc.2006-1009","article-title":"Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes","volume":"91","author":"Herman","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1124\/jpet.113.206466_bib14","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.2337\/diabetes.49.12.2063","article-title":"Mechanism by which metformin reduces glucose production in type 2 diabetes","volume":"49","author":"Hundal","year":"2000","journal-title":"Diabetes"},{"key":"10.1124\/jpet.113.206466_bib15","first-page":"156","article-title":"Effects of pioglitazone on glucose and lipid metabolism in normal and insulin resistant animals","volume":"40","author":"Ikeda","year":"1990","journal-title":"Arzneimittelforschung"},{"key":"10.1124\/jpet.113.206466_bib16","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nature01478","article-title":"Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40","volume":"422","author":"Itoh","year":"2003","journal-title":"Nature"},{"key":"10.1124\/jpet.113.206466_bib17","doi-asserted-by":"crossref","first-page":"696","DOI":"10.2337\/diacare.13.6.696","article-title":"Cellular mechanism of action of metformin","volume":"13","author":"Klip","year":"1990","journal-title":"Diabetes Care"},{"key":"10.1124\/jpet.113.206466_bib18","doi-asserted-by":"crossref","first-page":"e27270","DOI":"10.1371\/journal.pone.0027270","article-title":"AMG 837: a novel GPR40\/FFA1 agonist that enhances insulin secretion and lowers glucose levels in rodents","volume":"6","author":"Lin","year":"2011","journal-title":"PLoS ONE"},{"issue":"Suppl 3","key":"10.1124\/jpet.113.206466_bib19","doi-asserted-by":"crossref","first-page":"18","DOI":"10.2337\/diacare.13.3.18","article-title":"Sulfonylureas","volume":"13","author":"Melander","year":"1990","journal-title":"Why, which, and how? Diabetes Care"},{"key":"10.1124\/jpet.113.206466_bib20","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ejphar.2004.04.038","article-title":"Pharmacological characteristics of a novel nonthiazolidinedione insulin sensitizer, FK614","volume":"494","author":"Minoura","year":"2004","journal-title":"Eur J Pharmacol"},{"key":"10.1124\/jpet.113.206466_bib21","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.ejphar.2005.05.042","article-title":"Ameliorating effect of FK614, a novel nonthiazolidinedione peroxisome proliferator-activated receptor gamma agonist, on insulin resistance in Zucker fatty rat","volume":"519","author":"Minoura","year":"2005","journal-title":"Eur J Pharmacol"},{"key":"10.1124\/jpet.113.206466_bib22","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.2337\/db08-1233","article-title":"Overexpression of GPR40 in pancreatic beta-cells augments glucose-stimulated insulin secretion and improves glucose tolerance in normal and diabetic mice","volume":"58","author":"Nagasumi","year":"2009","journal-title":"Diabetes"},{"issue":"Suppl 1","key":"10.1124\/jpet.113.206466_bib23","first-page":"25","article-title":"Acute and chronic effects of sulfonylurea drugs on pancreatic islet function in man","volume":"7","author":"Pfeifer","year":"1984","journal-title":"Diabetes Care"},{"issue":"Suppl 2","key":"10.1124\/jpet.113.206466_bib24","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1007\/s001250051395","article-title":"Signal transduction mechanisms in nutrient-induced insulin secretion","volume":"40","author":"Prentki","year":"1997","journal-title":"Diabetologia"},{"key":"10.1124\/jpet.113.206466_bib25","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1475-2840-12-35","article-title":"Effects of sitagliptin beyond glycemic control: focus on quality of life","volume":"12","author":"Sakamoto","year":"2013","journal-title":"Cardiovasc Diabetol"},{"key":"10.1124\/jpet.113.206466_bib26","unstructured":"Smith U (2001) Pioglitazone: mechanism of action. Int J Clin Pract Suppl :13\u201318."},{"key":"10.1124\/jpet.113.206466_bib27","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/j.1749-6632.1959.tb44923.x","article-title":"Influences of glucose loading and of injected insulin on hepatic glucose output","volume":"82","author":"Steele","year":"1959","journal-title":"Ann N Y Acad Sci"},{"key":"10.1124\/jpet.113.206466_bib28","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.2337\/db08-0130","article-title":"Selective small-molecule agonists of G protein-coupled receptor 40 promote glucose-dependent insulin secretion and reduce blood glucose in mice","volume":"57","author":"Tan","year":"2008","journal-title":"Diabetes"},{"key":"10.1124\/jpet.113.206466_bib29","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/350516a0","article-title":"Activation of the beta 1 isozyme of phospholipase C by alpha subunits of the Gq class of G proteins","volume":"350","author":"Taylor","year":"1991","journal-title":"Nature"},{"key":"10.1124\/jpet.113.206466_bib30","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1124\/jpet.111.183772","article-title":"TAK-875, an orally available G protein-coupled receptor 40\/free fatty acid receptor 1 agonist, enhances glucose-dependent insulin secretion and improves both postprandial and fasting hyperglycemia in type 2 diabetic rats","volume":"339","author":"Tsujihata","year":"2011","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.113.206466_bib31","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/j.clinthera.2011.10.014","article-title":"Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24-week, randomized, open-label, parallel-group comparison","volume":"33","author":"Wang","year":"2011","journal-title":"Clin Ther"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524287395?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524287395?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.113.206466","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T20:16:16Z","timestamp":1739996176000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356524287395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["S0022356524287395"],"URL":"https:\/\/doi.org\/10.1124\/jpet.113.206466","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2013,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Chronic Treatment with Novel GPR40 Agonists Improve Whole-Body Glucose Metabolism Based on the Glucose-Dependent Insulin Secretion","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.113.206466","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2013 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}