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Title: Transcriptional regulatory factor X6 (Rfx6) increases gastric inhibitory polypeptide (GIP) expression in enteroendocrine K-cells and is involved in GIP hypersecretion in high fat diet-induced obesity.
Authors: Suzuki, Kazuyo  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-5716-5242 (unconfirmed)
Harada, Norio  kyouindb  KAKEN_id
Yamane, Shunsuke  kyouindb  KAKEN_id
Nakamura, Yasuhiko
Sasaki, Kazuki
Nasteska, Daniela
Joo, Erina
Shibue, Kimitaka
Harada, Takanari
Hamasaki, Akihiro
Toyoda, Kentaro
Nagashima, Kazuaki  kyouindb  KAKEN_id
Inagaki, Nobuya  kyouindb  KAKEN_id
Author's alias: 鈴木, 和代
稲垣, 暢也
Keywords: Gene Expression
Hormones
Intestine
Nutrition
Obesity
GIP
K-cell
Pdx1
Rfx6
Issue Date: 18-Jan-2013
Publisher: American Society for Biochemistry and Molecular Biology
Journal title: The Journal of biological chemistry
Volume: 288
Issue: 3
Start page: 1929
End page: 1938
Abstract: Gastric inhibitory polypeptide (GIP) is an incretin released from enteroendocrine K-cells in response to nutrient ingestion. GIP potentiates glucose-stimulated insulin secretion and induces energy accumulation into adipose tissue, resulting in obesity. Plasma GIP levels are reported to be increased in the obese state. However, the molecular mechanisms of GIP secretion and high fat diet (HFD)-induced GIP hypersecretion remain unclear, primarily due to difficulties in separating K-cells from other intestinal epithelial cells in vivo. In this study, GIP-GFP knock-in mice that enable us to visualize K-cells by enhanced GFP were established. Microarray analysis of isolated K-cells from these mice revealed that transcriptional regulatory factor X6 (Rfx6) is expressed exclusively in K-cells. In vitro experiments using the mouse intestinal cell line STC-1 showed that knockdown of Rfx6 decreased mRNA expression, cellular content, and secretion of GIP. Rfx6 bound to the region in the gip promoter that regulates gip promoter activity, and overexpression of Rfx6 increased GIP mRNA expression. HFD induced obesity and GIP hypersecretion in GIP-GFP heterozygous mice in vivo. Immunohistochemical and flow cytometry analysis showed no significant difference in K-cell number between control fat diet-fed (CFD) and HFD-fed mice. However, GIP content in the upper small intestine and GIP mRNA expression in K-cells were significantly increased in HFD-fed mice compared with those in CFD-fed mice. Furthermore, expression levels of Rfx6 mRNA were increased in K-cells of HFD-fed mice. These results suggest that Rfx6 increases GIP expression and content in K-cells and is involved in GIP hypersecretion in HFD-induced obesity.
Rights: © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。This is not the published version. Please cite only the published version.
URI: http://hdl.handle.net/2433/182055
DOI(Published Version): 10.1074/jbc.M112.423137
PubMed ID: 23192339
Appears in Collections:Journal Articles

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