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Title: Oral Administration of Apple Procyanidins Ameliorates Insulin Resistance via Suppression of Pro-inflammatory Cytokines Expression in Liver of Diabetic ob/ob Mice
Authors: Ogura, Kasane
Ogura, Masahito  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-7107-2752 (unconfirmed)
Shoji, Toshihiko
Sato, Yuichi
Tahara, Yumiko
Yamano, Gen
Sato, Hiroki
Sugizaki, Kazu
Fujita, Naotaka
Tatsuoka, Hisato  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-0669-6825 (unconfirmed)
Usui, Ryota  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-4641-0158 (unconfirmed)
Mukai, Eri
Fujimoto, Shimpei
Inagaki, Nobuya  kyouindb  KAKEN_id
Nagashima, Kazuaki
Author's alias: 長嶋, 一昭
稲垣, 暢也
Keywords: apple procyanidins
insulin resistance
inflammation
ob/ob mouse
Issue Date: 23-Nov-2016
Publisher: American Chemical Society (ACS)
Journal title: Journal of Agricultural and Food Chemistry
Volume: 64
Issue: 46
Start page: 8857
End page: 8865
Abstract: Genetic factors are important determinants of the onset and progression of diabetes mellitus. Numerous susceptibility genes for type 2 diabetes, including potassium voltage-gated channel, KQT-like subfamily Q, member1 (KCNQ1), have been identified in humans by genome-wide analyses and other studies. Experiments with genetically modified mice have also implicated various genes in the pathogenesis of diabetes. However, the possible effects of the parent of origin for diabetes susceptibility alleles on disease onset have remained unclear. Here, we show that a mutation at the Kcnq1 locus reduces pancreatic β-cell mass in mice by epigenetic modulation only when it is inherited from the father. The noncoding RNA KCNQ1 overlapping transcript1 (Kcnq1ot1) is expressed from the Kcnq1 locus and regulates the expression of neighboring genes on the paternal allele. We found that disruption of Kcnq1 results in reduced Kcnq1ot1 expression as well as the increased expression of cyclin-dependent kinase inhibitor 1C (Cdkn1c), an imprinted gene that encodes a cell cycle inhibitor, only when the mutation is on the paternal allele. Furthermore, histone modification at the Cdkn1c promoter region in pancreatic islets was found to contribute to this phenomenon. Our observations suggest that the Kcnq1 genomic region directly regulates pancreatic β-cell mass and that genomic imprinting may be a determinant of the onset of diabetes mellitus.
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Agricultural and Food Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.jafc.6b03424.
The full-text file will be made open to the public on 23 Nov. 2017 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version. 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。
URI: http://hdl.handle.net/2433/217455
DOI(Published Version): 10.1021/acs.jafc.6b03424
PubMed ID: 27792335
Appears in Collections:Journal Articles

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