Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Species-specific action of (Pro3)GIP - a full agonist at human GIP receptors, but a partial agonist and competitive antagonist at rat and mouse GIP receptors

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Metabolic control and sex: A focus on inflammatory-linked mediators

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  2. Different mechanisms involved in liraglutide and glucagon-like peptide-1 vasodilatation in rat mesenteric small arteries

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Characterization of binding, functional activity, and contractile responses of the selective 5-HT1F receptor agonist lasmiditan

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. The Glucagon Receptor Antagonist LY2409021 has No Effect on Postprandial Glucose in Type 2 Diabetes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Vitamin D supplementation improves fasting insulin levels and HDL cholesterol in infertile men

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Glucagon Clearance is Preserved in Type 2 Diabetes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

BACKGROUND AND PURPOSE: Specific, high potency receptor antagonists are valuable tools when evaluating animal and human physiology. Within the glucose-dependent, insulinotropic polypeptide (GIP) system, considerable attention has been given to the presumed GIP receptor antagonist, (Pro3)GIP, and its effect in murine studies. We conducted a pharmacological analysis of this ligand including interspecies differences between the rodent and human GIP system.

EXPERIMENTAL APPROACH: Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation and assayed in competition binding using (125) I-human GIP. Using isolated perfused pancreata both from wild type and GIP receptor-deficient rodents, insulin-releasing, glucagon-releasing and somatostatin-releasing properties in response to species-specific GIP and (Pro3)GIP analogues were evaluated.

KEY RESULTS: Human (Pro3)GIP is a full agonist at human GIP receptors with similar efficacy (Emax ) for cAMP production as human GIP, while both rat and mouse(Pro3)GIP were partial agonists on their corresponding receptors. Rodent GIPs are more potent and efficacious at their receptors than human GIP. In perfused pancreata in the presence of 7 mM glucose, both rodent (Pro3)GIP analogues induced modest insulin, glucagon and somatostatin secretion, corresponding to the partial agonist activities observed in cAMP production.

CONCLUSIONS AND IMPLICATIONS: When evaluating new compounds, it is important to consider interspecies differences both at the receptor and ligand level. Thus, in rodent models, human GIP is a comparatively weak partial agonist. Human (Pro3)GIP was not an antagonist at human GIP receptors, so there is still a need for a potent antagonist in order to elucidate the physiology of human GIP.

OriginalsprogEngelsk
TidsskriftBritish Journal of Pharmacology
Vol/bind173
Udgave nummer1
Sider (fra-til)27-38
Antal sider12
ISSN0007-1188
DOI
StatusUdgivet - jan. 2016

ID: 45902320