{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:49:08Z","timestamp":1792518548594,"version":"4.5.0"},"reference-count":32,"publisher":"American Diabetes Association","issue":"9","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,9,1]]},"abstract":"<jats:p>OBJECTIVE\u2014The G-protein\u2013coupled receptor Gpr40 is expressed in \u03b2-cells where it contributes to free fatty acid (FFA) enhancement of glucose-stimulated insulin secretion (1\u20134). However, other sites of Gpr40 expression, including the intestine, have been suggested. The transcription factor IPF1\/PDX1 was recently shown to bind to an enhancer element within the 5\u2032-flanking region of Gpr40 (5), implying that IPF1\/PDX1 might regulate Gpr40 expression. Here, we addressed whether 1) Gpr40 is expressed in the intestine and 2) Ipf1\/Pdx1 function is required for Gpr40 expression.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014In the present study, Gpr40 expression was monitored by X-gal staining using Gpr40 reporter mice and by in situ hybridization. Ipf1\/Pdx1-null and \u03b2-cell specific mutants were used to investigate whether Ipf1\/Pdx1 controls Gpr40 expression. Plasma insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucose levels in response to acute oral fat diet were determined in Gpr40 mutant and control mice.<\/jats:p>\n               <jats:p>RESULTS\u2014Here, we show that Gpr40 is expressed in endocrine cells of the gastrointestinal tract, including cells expressing the incretin hormones GLP-1 and GIP, and that Gpr40 mediates FFA-stimulated incretin secretion. We also show that Ipf1\/Pdx1 is required for expression of Gpr40 in \u03b2-cells and endocrine cells of the anterior gastrointestinal tract.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014Together, our data provide evidence that Gpr40 modulates FFA-stimulated insulin secretion from \u03b2-cells not only directly but also indirectly via regulation of incretin secretion. Moreover, our data suggest a conserved role for Ipf1\/Pdx1 and Gpr40 in FFA-mediated secretion of hormones that regulate glucose and overall energy homeostasis.<\/jats:p>","DOI":"10.2337\/db08-0307","type":"journal-article","created":{"date-parts":[[2008,6,3]],"date-time":"2008-06-03T00:58:30Z","timestamp":1212454710000},"page":"2280-2287","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":541,"title":["<i>Gpr40<\/i> Is Expressed in Enteroendocrine Cells and Mediates Free Fatty Acid Stimulation of Incretin Secretion"],"prefix":"10.2337","volume":"57","author":[{"given":"Sara","family":"Edfalk","sequence":"first","affiliation":[{"name":"From the Umea\u030a Center for Molecular Medicine, University of Umea\u030a, Umea\u030a, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pa\u0308r","family":"Steneberg","sequence":"additional","affiliation":[{"name":"From the Umea\u030a Center for Molecular Medicine, University of Umea\u030a, Umea\u030a, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Edlund","sequence":"additional","affiliation":[{"name":"From the Umea\u030a Center for Molecular Medicine, University of Umea\u030a, Umea\u030a, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031210123376300_R1","doi-asserted-by":"crossref","unstructured":"Itoh Y, Kawamata Y, Harada M, Kobayashi M, Fujii R, Fukusumi S, Ogi K, Hosoya M, Tanaka Y, Uejima H, Tanaka H, Maruyama M, Satoh R, Okubo S, Kizawa H, Komatsu H, Matsumura F, Noguchi Y, Shinohara T, Hinuma S, Fujisawa Y, Fujino M: Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. 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