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Pharmacokinetics of exogenous GIP(1-42) in C57Bl/6 mice; Extremely rapid degradation but marked variation between available assays.

Authors
  • Boer, Geke Aline1
  • Hartmann, Bolette2
  • Holst, Jens Juul3
  • 1 NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: [email protected] , (Denmark)
  • 2 NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: [email protected] , (Denmark)
  • 3 NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: [email protected] , (Denmark)
Type
Published Article
Journal
Peptides
Publication Date
Nov 24, 2020
Volume
136
Pages
170457–170457
Identifiers
DOI: 10.1016/j.peptides.2020.170457
PMID: 33245951
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Like other peptide hormones, glucose-dependent insulinotropic polypeptide (GIP) is rapidly cleared from the circulation. Dipeptidyl peptidase-4 (DPP-4) is known to be involved. Information on the overall pharmacokinetics of GIP in rodents is, however, lacking. We investigated the pharmacokinetics of exogenous GIP after intravenous, subcutaneous and intraperitoneal injection with and without DPP-4 inhibition in conscious female C57Bl/6 mice. Secondly, we compared total and intact GIP levels measured by an in-house RIA and commercially available ELISA kits to determine the suitability of these methods for in vivo and in vitro measurements. GIP half-life following intravenous injection amounted to 93 ± 2 s, which was extended to 5 ± 0.6 min by inhibition of DPP-4. Intact GIP levels following subcutaneous and intraperitoneal GIP administration were approximately 15 % of total GIP. The area under the curve of intact GIP (GIP exposure) following GIP injection was significantly increased by DPP-4 inhibition, whereas total GIP levels remained unchanged. We found significant variation between measurements of total, but not intact GIP performed with our in-house RIA and ELISAs in samples obtained after in vivo administration of GIP. Different preanalytical sample preparation (EDTA plasma, heparin plasma, assay buffer and PBS) significantly influenced results for all ELISA kits used. Thus, in experiments involving exogenous GIP(1-42) administration in mice, it is important to consider that this will result in a very low ratio of intact:total peptide but co-administration of a DPP-4 inhibitor greatly elevates this ratio. Furthermore, for comparison of GIP levels, it is essential to maintain uniformity concerning assay methodology and sample preparation. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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