Pharmacokinetics of exogenous GIP(1-42) in C57Bl/6 mice; Extremely rapid degradation but marked variation between available assays
| Autor: | Bolette Hartmann, Geke Aline Boer, Jens J. Holst |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Blood Glucose
C57BL/6 DDP-4 Physiology medicine.medical_treatment Peptide Biochemistry Mice 0302 clinical medicine Endocrinology Glucagon-Like Peptide 1 GIP ELISA chemistry.chemical_classification GIP biology Chemistry Area under the curve GIP glucose-dependent insulinotropic polypeptide ELISA enzyme-linked immunosorbent assay Female IP intraperitoneal IV intravenous hormones hormone substitutes and hormone antagonists endocrine system medicine.medical_specialty Peptide degradation Dipeptidyl Peptidase 4 Intraperitoneal injection 030209 endocrinology & metabolism Gastric Inhibitory Polypeptide Peptide hormone Article Receptors Gastrointestinal Hormone 03 medical and health sciences Cellular and Molecular Neuroscience Pharmacokinetics In vivo Internal medicine medicine Animals Humans Hypoglycemic Agents GPCR G protein-coupled receptor Dipeptidyl-Peptidase IV Inhibitors GIPR glucose-dependent insulinotropic polypeptide receptor DPP-4 dipeptidyl peptidase-4 Glucagon biology.organism_classification Hypoglycemia Peptide Fragments In vitro SC subcutaneous RIA radioimmunoassays Proteolysis PC1/3 prohormone convertase 1/3 030217 neurology & neurosurgery |
| Zdroj: | Boer, G A, Hartmann, B & Holst, J J 2021, ' Pharmacokinetics of exogenous GIP(1-42) in C57Bl/6 mice; Extremely rapid degradation but marked variation between available assays ', Peptides, vol. 136, 170457 . https://doi.org/10.1016/j.peptides.2020.170457 Peptides |
| ISSN: | 0196-9781 |
| Popis: | Highlights • Peptide hormone GIP shows an extremely short half-life of 90 s in mice. • Administration of GIP yields a very low ratio of intact:total peptide. • Co-administration with DPP-4 inhibitors increases the half-life of GIP to 4 min. • We highly recommend DPP-4 inhibition in future experiments utilizing exogenous GIP. 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. |
| Databáze: | OpenAIRE |
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