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
| Autor: | Hideaki Kaneto, Hidenori Hirukawa, Tomohiko Kimura, Kenji Kohara, Tomoatsu Mune, Kohei Kaku, Seizo Okauchi, Masashi Shimoda, Saeko Moriuchi, Atsushi Obata |
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| Rok vydání: | 2018 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Small interfering RNA Endocrinology Diabetes and Metabolism Regulator 030209 endocrinology & metabolism digestive system Cell Line Receptors G-Protein-Coupled 03 medical and health sciences Mice 0302 clinical medicine Endocrinology Free fatty acid receptor 1 Internal medicine Insulin-Secreting Cells Insulin Secretion medicine Animals Obesity RNA Messenger RNA Small Interfering Receptor Transcription factor Homeodomain Proteins Messenger RNA Chemistry Disease Models Animal Diabetes Mellitus Type 2 Cell culture 030220 oncology & carcinogenesis Trans-Activators PDX1 |
| Zdroj: | Endocrine journal. 66(1) |
| ISSN: | 1348-4540 |
| Popis: | 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 β-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 β-cell-related genes including insulin gene and thereby contributes to the maintenance of mature β-cell function. The aim of this study was to evaluate how Ffar1 expression in β-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 β-cell-derived cell line. As the results, Ffar1 mRNA and protein expression in β-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 β-cells. |
| Databáze: | OpenAIRE |
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