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大学・研究所にある論文を検索できる 「Receptor-Mediated Bioassay Reflects Dynamic Change of Glucose-Dependent Insulinotropic Polypeptide by Dipeptidyl Peptidase 4 Inhibitor Treatment in Subjects With Type 2 Diabetes.」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

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Receptor-Mediated Bioassay Reflects Dynamic Change of Glucose-Dependent Insulinotropic Polypeptide by Dipeptidyl Peptidase 4 Inhibitor Treatment in Subjects With Type 2 Diabetes.

YANAGIMACHI Tsuyoshi 20596275 FUJITA Yukihiro 20451461 0000-0003-3238-8743 TAKEDA Yasutaka HONJO Jun YOKOYAMA Hiroki HANEDA Masakazu 滋賀医科大学

2020.04.24

概要

Objective:
We recently observed a greater increase in plasma levels of bioactive glucose-dependent insulinotropic polypeptide (GIP) than glucagon-like peptide 1 (GLP-1) using the receptor-mediated bioassays in the subjects with normal glycemic tolerance (NGT) treated with dipeptidyl peptidase 4 (DPP-4) inhibitors, which may be unappreciated using conventional enzyme-linked immunosorbent assays (ELISAs) during oral glucose tolerance test. Thus, we determined incretin levels in addition to glucagon level using the bioassays in type 2 diabetes mellitus (T2DM) subjects with or without treatment of DPP-4 inhibitor, to evaluate whether these assays can accurately measure bioactivity of these peptides.
Methods:
We performed single meal tolerance test (MTT) by using a cookie meal (carbohydrate 75.0 g, protein 8.0 g, fat 28.5 g) in the subjects with NGT (n = 9), the subjects with T2DM treated without DPP-4 inhibitor (n = 7) and the subjects with T2DM treated with DPP-4 inhibitor (n = 10). All subjects fasted for 10-12 h before the MTT, and blood samples were collected at 0, 30, 60, and 120 min. We used the cell lines stably cotransfected with human-form GIP, GLP-1 or glucagon receptor, and a cyclic adenosine monophosphate-inducible luciferase expression construct for the bioassays. We measured active GIP, active GLP-1, and glucagon by the bioassays. To evaluate the efficacy of bioassay, we measured identical samples via ELISA kits.
Results:
During the single MTT study, postprandial active GIP bioassay levels of T2DM with DPP-4 inhibitor treatment were drastically higher than those of NGT and T2DM without DPP-4 inhibitor, although the DPP-4 inhibitor-treated group showed moderate increase of active GIPELISA and active GLP-1 bioassay , while active GLP-1 bioassay levels of T2DM subjects without DPP-4 inhibitor were comparable to those of NGT subjects. During the serial MTT, administration of DPP-4 inhibitor significantly increased active GIP bioassay levels, but not active GLP-1 bioassay .
Conclusions:
In comparison to conventional ELISA, receptor-mediated bioassay reflects dynamic change of GIP polypeptide by DPP-4 inhibitor treatment in subjects with type 2 diabetes.

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Conflict of Interest: The authors declare that the research was conducted in the

absence of any commercial or financial relationships that could be construed as a

potential conflict of interest.

Copyright © 2020 Yanagimachi, Fujita, Takeda, Honjo, Yokoyama and Haneda.

This is an open-access article distributed under the terms of the Creative Commons

Attribution License (CC BY). The use, distribution or reproduction in other forums

is permitted, provided the original author(s) and the copyright owner(s) are credited

and that the original publication in this journal is cited, in accordance with accepted

academic practice. No use, distribution or reproduction is permitted which does not

comply with these terms.

April 2020 | Volume 11 | Article 214

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