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Gpr40 is expressed ...
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Edfalk, SaraUmeå universitet,Umeå centrum för molekylär medicin (UCMM),Edlund Helena
(författare)
Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion.
- Artikel/kapitelEngelska2008
Förlag, utgivningsår, omfång ...
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American Diabetes Association,2008
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LIBRIS-ID:oai:DiVA.org:umu-23321
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-23321URI
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https://doi.org/10.2337/db08-0307DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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OBJECTIVE: The G-protein-coupled receptor Gpr40 is expressed in beta-cells where it contributes to free fatty acid (FFA) enhancement of glucose-stimulated insulin secretion. 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'-flanking region of Gpr40, 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. RESEARCH DESIGN AND METHODS: In the present study, Gpr40 expression was monitored by X-gal staining using Gpr40 reporter mice and by in situ hybridization. Ipf1/Pdx1-null and beta-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. RESULTS: Here, 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 beta-cells and endocrine cells of the anterior gastrointestinal tract. CONCLUSIONS: Together, our data provide evidence that Gpr40 modulates FFA-stimulated insulin secretion from beta-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.
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Steneberg, PärUmeå universitet,Umeå centrum för molekylär medicin (UCMM),Edlund Helena(Swepub:umu)past0002
(författare)
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Edlund, Helena,1960-Umeå universitet,Umeå centrum för molekylär medicin (UCMM),Edlund Helena(Swepub:umu)heed0001
(författare)
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Umeå universitetUmeå centrum för molekylär medicin (UCMM)
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Diabetes: American Diabetes Association57:9, s. 2280-71939-327X0012-1797
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Diabetes
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