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Publication : Suppression of free fatty acid receptor 1 expression in pancreatic β-cells in obese type 2 diabetic db/db mice: a potential role of pancreatic and duodenal homeobox factor 1.

First Author  Kohara K Year  2019
Journal  Endocr J Volume  66
Issue  1 Pages  43-50
PubMed ID  30333365 Mgi Jnum  J:295664
Mgi Id  MGI:6454197 Doi  10.1507/endocrj.EJ18-0203
Citation  Kohara K, et al. (2019) Suppression of free fatty acid receptor 1 expression in pancreatic beta-cells in obese type 2 diabetic db/db mice: a potential role of pancreatic and duodenal homeobox factor 1. Endocr J 66(1):43-50
abstractText  It is known that long-chain fatty acids bind to free fatty acid receptor 1 (Ffar1), also known as G protein-coupled receptor 40 (GPR40), and amplify glucose-stimulated insulin secretion (GSIS) from pancreatic beta-cells and that Ffar1 agonists facilitates insulin secretion and ameliorates glycemic control. On the other hands, pancreatic and duodenal homeobox factor 1 (Pdx1) is an important transcription factor for various beta-cell-related genes including insulin gene and thereby contributes to the maintenance of mature beta-cell function. The aim of this study was to evaluate how Ffar1 expression in beta-cells is altered under diabetic conditions. In this study, we used male obese type 2 diabetic mice and control mice. We evaluated Ffar1 and Pdx1 mRNA and protein expression levels in both mice. In addition, we examined whether Pdx1 is a possible regulator of Ffar1 expression using small interfering RNA for Pdx1 (siPdx1) in beta-cell-derived cell line. As the results, Ffar1 mRNA and protein expression in beta-cells were significantly lower in obese type 2 diabetic db/db mice compared to control mice which was accompanied by the decreased expression of Pdx1. In addition, down-regulation of Pdx1 expression using siPdx1 suppressed Ffar1 expression. Furthermore, adenoviral Pdx1 overexpression significantly increased Ffar1 expression. In conclusion, Ffar1 expression is markedly down-regulated under diabetic conditions which is accompanied by decreased expression of Pdx1. Furthermore, it is likely that Pdx1 is a regulator of Ffar1 expression in beta-cells.
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