GIP(3-30)NH2 is a potent competitive antagonist of the GIP receptor and effectively inhibits GIP-mediated insulin, glucagon, and somatostatin release

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Standard

GIP(3-30)NH2 is a potent competitive antagonist of the GIP receptor and effectively inhibits GIP-mediated insulin, glucagon, and somatostatin release. / Sparre-Ulrich, A H; Gabe, M N; Gasbjerg, L S; Christiansen, C B; Svendsen, B; Hartmann, B; Holst, J J; Rosenkilde, M M.

I: Biochemical Pharmacology, Bind 131, 2017, s. 78-88.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Sparre-Ulrich, AH, Gabe, MN, Gasbjerg, LS, Christiansen, CB, Svendsen, B, Hartmann, B, Holst, JJ & Rosenkilde, MM 2017, 'GIP(3-30)NH2 is a potent competitive antagonist of the GIP receptor and effectively inhibits GIP-mediated insulin, glucagon, and somatostatin release', Biochemical Pharmacology, bind 131, s. 78-88. https://doi.org/10.1016/j.bcp.2017.02.012

APA

Sparre-Ulrich, A. H., Gabe, M. N., Gasbjerg, L. S., Christiansen, C. B., Svendsen, B., Hartmann, B., ... Rosenkilde, M. M. (2017). GIP(3-30)NH2 is a potent competitive antagonist of the GIP receptor and effectively inhibits GIP-mediated insulin, glucagon, and somatostatin release. Biochemical Pharmacology, 131, 78-88. https://doi.org/10.1016/j.bcp.2017.02.012

Vancouver

Sparre-Ulrich AH, Gabe MN, Gasbjerg LS, Christiansen CB, Svendsen B, Hartmann B o.a. GIP(3-30)NH2 is a potent competitive antagonist of the GIP receptor and effectively inhibits GIP-mediated insulin, glucagon, and somatostatin release. Biochemical Pharmacology. 2017;131:78-88. https://doi.org/10.1016/j.bcp.2017.02.012

Author

Sparre-Ulrich, A H ; Gabe, M N ; Gasbjerg, L S ; Christiansen, C B ; Svendsen, B ; Hartmann, B ; Holst, J J ; Rosenkilde, M M. / GIP(3-30)NH2 is a potent competitive antagonist of the GIP receptor and effectively inhibits GIP-mediated insulin, glucagon, and somatostatin release. I: Biochemical Pharmacology. 2017 ; Bind 131. s. 78-88.

Bibtex

@article{e3003660d4794e00b8e1c91aa921b50c,
title = "GIP(3-30)NH2 is a potent competitive antagonist of the GIP receptor and effectively inhibits GIP-mediated insulin, glucagon, and somatostatin release",
abstract = "Alternative processing of the precursor protein pro-GIP results in endogenously produced GIP(1-30)NH2, that by DPP-4 cleavage in vivo results in the metabolite GIP(3-30)NH2. We showed previously that GIP(3-30)NH2 is a high affinity antagonist of the human GIPR in vitro. Here we determine whether it is suitable for studies of GIP physiology in rats since effects of GIP agonists and antagonists are strictly species-dependent. Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation or assayed in competition binding using human (125)I-GIP(1-42) as radioligand. In isolated perfused rat pancreata, insulin, glucagon, and somatostatin-releasing properties were evaluated. Competition binding demonstrated that on the rat GIP receptor (GIPR), rat GIP(3-30)NH2 bound with high affinity (Ki of 17nM), in contrast to human GIP(3-30)NH2 (Ki of 250nM). In cAMP studies, rat GIP(3-30)NH2 inhibited GIP(1-42)-induced rat GIPR activation and schild-plot analysis showed competitive antagonism with a pA2 of 13nM and a slope of 0.9±0.09. Alone, rat GIP(3-30)NH2 displayed weak, low-potent partial agonistic properties (EC50>1μM) with an efficacy of 9.4{\%} at 0.32μM compared to GIP(1-42). In perfused rat pancreata, rat GIP(3-30)NH2 efficiently antagonized rat GIP(1-42)-induced insulin, somatostatin, and glucagon secretion. In summary, rat GIP(3-30)NH2 is a high affinity competitive GIPR antagonist and effectively antagonizes GIP-mediated G protein-signaling as well as pancreatic hormone release, while human GIP(3-30)NH2, despite a difference of only one amino acid between the two (arginine in position 18 in rat GIP(3-30)NH2; histidine in human), is unsuitable in the rat system. This underlines the importance of species differences in the GIP system, and the limitations of testing human peptides in rodent systems.",
author = "Sparre-Ulrich, {A H} and Gabe, {M N} and Gasbjerg, {L S} and Christiansen, {C B} and B Svendsen and B Hartmann and Holst, {J J} and Rosenkilde, {M M}",
note = "Copyright {\circledC} 2017 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2017",
doi = "10.1016/j.bcp.2017.02.012",
language = "English",
volume = "131",
pages = "78--88",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - GIP(3-30)NH2 is a potent competitive antagonist of the GIP receptor and effectively inhibits GIP-mediated insulin, glucagon, and somatostatin release

AU - Sparre-Ulrich, A H

AU - Gabe, M N

AU - Gasbjerg, L S

AU - Christiansen, C B

AU - Svendsen, B

AU - Hartmann, B

AU - Holst, J J

AU - Rosenkilde, M M

N1 - Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2017

Y1 - 2017

N2 - Alternative processing of the precursor protein pro-GIP results in endogenously produced GIP(1-30)NH2, that by DPP-4 cleavage in vivo results in the metabolite GIP(3-30)NH2. We showed previously that GIP(3-30)NH2 is a high affinity antagonist of the human GIPR in vitro. Here we determine whether it is suitable for studies of GIP physiology in rats since effects of GIP agonists and antagonists are strictly species-dependent. Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation or assayed in competition binding using human (125)I-GIP(1-42) as radioligand. In isolated perfused rat pancreata, insulin, glucagon, and somatostatin-releasing properties were evaluated. Competition binding demonstrated that on the rat GIP receptor (GIPR), rat GIP(3-30)NH2 bound with high affinity (Ki of 17nM), in contrast to human GIP(3-30)NH2 (Ki of 250nM). In cAMP studies, rat GIP(3-30)NH2 inhibited GIP(1-42)-induced rat GIPR activation and schild-plot analysis showed competitive antagonism with a pA2 of 13nM and a slope of 0.9±0.09. Alone, rat GIP(3-30)NH2 displayed weak, low-potent partial agonistic properties (EC50>1μM) with an efficacy of 9.4% at 0.32μM compared to GIP(1-42). In perfused rat pancreata, rat GIP(3-30)NH2 efficiently antagonized rat GIP(1-42)-induced insulin, somatostatin, and glucagon secretion. In summary, rat GIP(3-30)NH2 is a high affinity competitive GIPR antagonist and effectively antagonizes GIP-mediated G protein-signaling as well as pancreatic hormone release, while human GIP(3-30)NH2, despite a difference of only one amino acid between the two (arginine in position 18 in rat GIP(3-30)NH2; histidine in human), is unsuitable in the rat system. This underlines the importance of species differences in the GIP system, and the limitations of testing human peptides in rodent systems.

AB - Alternative processing of the precursor protein pro-GIP results in endogenously produced GIP(1-30)NH2, that by DPP-4 cleavage in vivo results in the metabolite GIP(3-30)NH2. We showed previously that GIP(3-30)NH2 is a high affinity antagonist of the human GIPR in vitro. Here we determine whether it is suitable for studies of GIP physiology in rats since effects of GIP agonists and antagonists are strictly species-dependent. Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation or assayed in competition binding using human (125)I-GIP(1-42) as radioligand. In isolated perfused rat pancreata, insulin, glucagon, and somatostatin-releasing properties were evaluated. Competition binding demonstrated that on the rat GIP receptor (GIPR), rat GIP(3-30)NH2 bound with high affinity (Ki of 17nM), in contrast to human GIP(3-30)NH2 (Ki of 250nM). In cAMP studies, rat GIP(3-30)NH2 inhibited GIP(1-42)-induced rat GIPR activation and schild-plot analysis showed competitive antagonism with a pA2 of 13nM and a slope of 0.9±0.09. Alone, rat GIP(3-30)NH2 displayed weak, low-potent partial agonistic properties (EC50>1μM) with an efficacy of 9.4% at 0.32μM compared to GIP(1-42). In perfused rat pancreata, rat GIP(3-30)NH2 efficiently antagonized rat GIP(1-42)-induced insulin, somatostatin, and glucagon secretion. In summary, rat GIP(3-30)NH2 is a high affinity competitive GIPR antagonist and effectively antagonizes GIP-mediated G protein-signaling as well as pancreatic hormone release, while human GIP(3-30)NH2, despite a difference of only one amino acid between the two (arginine in position 18 in rat GIP(3-30)NH2; histidine in human), is unsuitable in the rat system. This underlines the importance of species differences in the GIP system, and the limitations of testing human peptides in rodent systems.

U2 - 10.1016/j.bcp.2017.02.012

DO - 10.1016/j.bcp.2017.02.012

M3 - Journal article

VL - 131

SP - 78

EP - 88

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

ER -

ID: 174399897