PMID- 32390941
OWN - NLM
STAT- MEDLINE
DCOM- 20210528
LR  - 20221207
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 11
DP  - 2020
TI  - Receptor-Mediated Bioassay Reflects Dynamic Change of Glucose-Dependent 
      Insulinotropic Polypeptide by Dipeptidyl Peptidase 4 Inhibitor Treatment in 
      Subjects With Type 2 Diabetes.
PG  - 214
LID - 10.3389/fendo.2020.00214 [doi]
LID - 214
AB  - 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 GIP(ELISA) 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.
CI  - Copyright (c) 2020 Yanagimachi, Fujita, Takeda, Honjo, Yokoyama and Haneda.
FAU - Yanagimachi, Tsuyoshi
AU  - Yanagimachi T
AD  - Division of Metabolism and Biosystemic Science, Department of Internal Medicine, 
      Asahikawa Medical University, Asahikawa, Japan.
FAU - Fujita, Yukihiro
AU  - Fujita Y
AD  - Division of Metabolism and Biosystemic Science, Department of Internal Medicine, 
      Asahikawa Medical University, Asahikawa, Japan.
AD  - Department of Diabetology, Endocrinology and Nephrology, Department of Internal 
      Medicine, Shiga University of Medical Science, Otsu, Japan.
FAU - Takeda, Yasutaka
AU  - Takeda Y
AD  - Division of Metabolism and Biosystemic Science, Department of Internal Medicine, 
      Asahikawa Medical University, Asahikawa, Japan.
FAU - Honjo, Jun
AU  - Honjo J
AD  - Division of Metabolism and Biosystemic Science, Department of Internal Medicine, 
      Asahikawa Medical University, Asahikawa, Japan.
AD  - Jiyugaoka Medical Clinic, Internal Medicine, Obihiro, Japan.
FAU - Yokoyama, Hiroki
AU  - Yokoyama H
AD  - Jiyugaoka Medical Clinic, Internal Medicine, Obihiro, Japan.
FAU - Haneda, Masakazu
AU  - Haneda M
AD  - Division of Metabolism and Biosystemic Science, Department of Internal Medicine, 
      Asahikawa Medical University, Asahikawa, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200424
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Receptors, Gastrointestinal Hormone)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9007-92-5 (Glucagon)
RN  - D6H00MV7K8 (gastric inhibitory polypeptide receptor)
SB  - IM
MH  - Aged
MH  - Biological Assay
MH  - Biomarkers/*blood
MH  - Blood Glucose/analysis
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/*blood/drug therapy/pathology
MH  - Dipeptidyl-Peptidase IV Inhibitors/*administration & dosage
MH  - Female
MH  - Follow-Up Studies
MH  - Gastric Inhibitory Polypeptide/*blood
MH  - Glucagon/*blood
MH  - Glucagon-Like Peptide 1/*blood
MH  - Glucose Tolerance Test
MH  - Glycated Hemoglobin/analysis
MH  - Humans
MH  - Male
MH  - Prognosis
MH  - Receptors, Gastrointestinal Hormone/*blood
PMC - PMC7193081
OTO - NOTNLM
OT  - dipeptidyl peptidase 4
OT  - glucagon
OT  - glucagon-like peptide 1
OT  - glucose-dependent insulinotropic polypeptide
OT  - receptor-mediated bioassay
EDAT- 2020/05/12 06:00
MHDA- 2021/05/29 06:00
PMCR- 2020/01/01
CRDT- 2020/05/12 06:00
PHST- 2019/12/06 00:00 [received]
PHST- 2020/03/25 00:00 [accepted]
PHST- 2020/05/12 06:00 [entrez]
PHST- 2020/05/12 06:00 [pubmed]
PHST- 2021/05/29 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2020.00214 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2020 Apr 24;11:214. doi: 10.3389/fendo.2020.00214. 
      eCollection 2020.