Access count of this item: 153

Files in This Item:
File Description SizeFormat 
srep26375.pdf1.01 MBAdobe PDFView/Open
Title: Prevention of antipsychotic-induced hyperglycaemia by vitamin D: a data mining prediction followed by experimental exploration of the molecular mechanism.
Authors: Nagashima, Takuya
Shirakawa, Hisashi  kyouindb  KAKEN_id
Nakagawa, Takayuki  kyouindb  KAKEN_id
Kaneko, Shuji  kyouindb  KAKEN_id
Author's alias: 長島, 卓也
金子, 周司
Issue Date: 20-May-2016
Publisher: Nature Publishing Group
Journal title: Scientific reports
Volume: 6
Thesis number: 26375
Abstract: Atypical antipsychotics are associated with an increased risk of hyperglycaemia, thus limiting their clinical use. This study focused on finding the molecular mechanism underlying antipsychotic-induced hyperglycaemia. First, we searched for drug combinations in the FDA Adverse Event Reporting System (FAERS) database wherein a coexisting drug reduced the hyperglycaemia risk of atypical antipsychotics, and found that a combination with vitamin D analogues significantly decreased the occurrence of quetiapine-induced adverse events relating diabetes mellitus in FAERS. Experimental validation using mice revealed that quetiapine acutely caused insulin resistance, which was mitigated by dietary supplementation with cholecalciferol. Further database analysis of the relevant signalling pathway and gene expression predicted quetiapine-induced downregulation of Pik3r1, a critical gene acting downstream of insulin receptor. Focusing on the phosphatidylinositol 3-kinase (PI3K) signalling pathway, we found that the reduced expression of Pik3r1 mRNA was reversed by cholecalciferol supplementation in skeletal muscle, and that insulin-stimulated glucose uptake into C2C12 myotube was inhibited in the presence of quetiapine, which was reversed by concomitant calcitriol in a PI3K-dependent manner. Taken together, these results suggest that vitamin D coadministration prevents antipsychotic-induced hyperglycaemia and insulin resistance by upregulation of PI3K function.
Description: 有害事象ビッグデータから副作用の分子メカニズムを解明-統合失調症治療薬が起こす高血糖はビタミンDで防止できる. 京都大学プレスリリース. 2016-05-23.
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
URI: http://hdl.handle.net/2433/212474
DOI(Published Version): 10.1038/srep26375
PubMed ID: 27199286
Related Link: http://www.kyoto-u.ac.jp/ja/research/research_results/2016/160523_2.html
Appears in Collections:Journal Articles

Show full item record

Export to RefWorks


Export Format: 


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.