GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations.

Research output: Contribution to journalJournal articleResearchpeer-review

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GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations. / Deacon, Carolyn F; Plamboeck, Astrid; Rosenkilde, Mette M; de Heer, Jocelyn; Holst, Jens J.

In: American Journal of Physiology: Endocrinology and Metabolism, Vol. 291, No. 3, 2006, p. E468-75.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Deacon, CF, Plamboeck, A, Rosenkilde, MM, de Heer, J & Holst, JJ 2006, 'GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations.', American Journal of Physiology: Endocrinology and Metabolism, vol. 291, no. 3, pp. E468-75. https://doi.org/10.1152/ajpendo.00577.2005

APA

Deacon, C. F., Plamboeck, A., Rosenkilde, M. M., de Heer, J., & Holst, J. J. (2006). GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations. American Journal of Physiology: Endocrinology and Metabolism, 291(3), E468-75. https://doi.org/10.1152/ajpendo.00577.2005

Vancouver

Deacon CF, Plamboeck A, Rosenkilde MM, de Heer J, Holst JJ. GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations. American Journal of Physiology: Endocrinology and Metabolism. 2006;291(3):E468-75. https://doi.org/10.1152/ajpendo.00577.2005

Author

Deacon, Carolyn F ; Plamboeck, Astrid ; Rosenkilde, Mette M ; de Heer, Jocelyn ; Holst, Jens J. / GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations. In: American Journal of Physiology: Endocrinology and Metabolism. 2006 ; Vol. 291, No. 3. pp. E468-75.

Bibtex

@article{939deb80ab4b11ddb5e9000ea68e967b,
title = "GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations.",
abstract = "Glucose-dependent insulinotropic polypeptide [GIP-(1-42)] is degraded by dipeptidyl peptidase IV (DPP IV), forming GIP-(3-42). In mice, high concentrations of synthetic GIP-(3-42) may function as a GIP receptor antagonist, but it is unclear whether this occurs at physiological concentrations. In COS-7 cells transiently transfected with the human GIP receptor, GIP-(1-42) and -(3-42) bind with affinities (IC(50)) of 5.2 and 22 nM, respectively. GIP-(1-42) was a potent agonist, stimulating cAMP accumulation (EC(50), 13.5 pM); GIP-(3-42) alone had no effect. When incubated together with native GIP, GIP-(3-42) behaved as a weak antagonist (IC(50), 92 and 731 nM for inhibition of cAMP accumulation elicited by 10 pM and 1 nM native GIP, respectively). In the isolated perfused rat pancreas, GIP-(3-42) alone had no effect on insulin output and only reduced the response to GIP (1 nM) when coinfused in >50-fold molar excess (IC(50), 138 nM). The ability of GIP-(3-42) to affect the antihyperglycemic or insulinotropic actions of GIP-(1-42) was examined in chloralose-anesthetized pigs given intravenous glucose. Endogenous DPP IV activity was inhibited to reduce degradation of the infused GIP-(1-42), which was infused alone and together with GIP-(3-42), at rates sufficient to mimic postprandial concentrations of each peptide. Glucose, insulin, and glucagon responses were identical irrespective of whether GIP-(1-42) was infused alone or together with GIP-(3-42). We conclude that, although GIP-(3-42) can weakly antagonize cAMP accumulation and insulin output in vitro, it does not behave as a physiological antagonist in vivo.",
author = "Deacon, {Carolyn F} and Astrid Plamboeck and Rosenkilde, {Mette M} and {de Heer}, Jocelyn and Holst, {Jens J}",
note = "Keywords: Animals; Antigens, CD26; Binding, Competitive; Blood Glucose; COS Cells; Cercopithecus aethiops; Cyclic AMP; Enzyme Inhibitors; Gastric Inhibitory Polypeptide; Glucagon; Humans; Insulin; Male; Pancreas; Peptide Fragments; Perfusion; Pyrroles; Rats; Rats, Wistar; Receptors, Gastrointestinal Hormone; Swine; Valine",
year = "2006",
doi = "10.1152/ajpendo.00577.2005",
language = "English",
volume = "291",
pages = "E468--75",
journal = "American Journal of Physiology: Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "3",

}

RIS

TY - JOUR

T1 - GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations.

AU - Deacon, Carolyn F

AU - Plamboeck, Astrid

AU - Rosenkilde, Mette M

AU - de Heer, Jocelyn

AU - Holst, Jens J

N1 - Keywords: Animals; Antigens, CD26; Binding, Competitive; Blood Glucose; COS Cells; Cercopithecus aethiops; Cyclic AMP; Enzyme Inhibitors; Gastric Inhibitory Polypeptide; Glucagon; Humans; Insulin; Male; Pancreas; Peptide Fragments; Perfusion; Pyrroles; Rats; Rats, Wistar; Receptors, Gastrointestinal Hormone; Swine; Valine

PY - 2006

Y1 - 2006

N2 - Glucose-dependent insulinotropic polypeptide [GIP-(1-42)] is degraded by dipeptidyl peptidase IV (DPP IV), forming GIP-(3-42). In mice, high concentrations of synthetic GIP-(3-42) may function as a GIP receptor antagonist, but it is unclear whether this occurs at physiological concentrations. In COS-7 cells transiently transfected with the human GIP receptor, GIP-(1-42) and -(3-42) bind with affinities (IC(50)) of 5.2 and 22 nM, respectively. GIP-(1-42) was a potent agonist, stimulating cAMP accumulation (EC(50), 13.5 pM); GIP-(3-42) alone had no effect. When incubated together with native GIP, GIP-(3-42) behaved as a weak antagonist (IC(50), 92 and 731 nM for inhibition of cAMP accumulation elicited by 10 pM and 1 nM native GIP, respectively). In the isolated perfused rat pancreas, GIP-(3-42) alone had no effect on insulin output and only reduced the response to GIP (1 nM) when coinfused in >50-fold molar excess (IC(50), 138 nM). The ability of GIP-(3-42) to affect the antihyperglycemic or insulinotropic actions of GIP-(1-42) was examined in chloralose-anesthetized pigs given intravenous glucose. Endogenous DPP IV activity was inhibited to reduce degradation of the infused GIP-(1-42), which was infused alone and together with GIP-(3-42), at rates sufficient to mimic postprandial concentrations of each peptide. Glucose, insulin, and glucagon responses were identical irrespective of whether GIP-(1-42) was infused alone or together with GIP-(3-42). We conclude that, although GIP-(3-42) can weakly antagonize cAMP accumulation and insulin output in vitro, it does not behave as a physiological antagonist in vivo.

AB - Glucose-dependent insulinotropic polypeptide [GIP-(1-42)] is degraded by dipeptidyl peptidase IV (DPP IV), forming GIP-(3-42). In mice, high concentrations of synthetic GIP-(3-42) may function as a GIP receptor antagonist, but it is unclear whether this occurs at physiological concentrations. In COS-7 cells transiently transfected with the human GIP receptor, GIP-(1-42) and -(3-42) bind with affinities (IC(50)) of 5.2 and 22 nM, respectively. GIP-(1-42) was a potent agonist, stimulating cAMP accumulation (EC(50), 13.5 pM); GIP-(3-42) alone had no effect. When incubated together with native GIP, GIP-(3-42) behaved as a weak antagonist (IC(50), 92 and 731 nM for inhibition of cAMP accumulation elicited by 10 pM and 1 nM native GIP, respectively). In the isolated perfused rat pancreas, GIP-(3-42) alone had no effect on insulin output and only reduced the response to GIP (1 nM) when coinfused in >50-fold molar excess (IC(50), 138 nM). The ability of GIP-(3-42) to affect the antihyperglycemic or insulinotropic actions of GIP-(1-42) was examined in chloralose-anesthetized pigs given intravenous glucose. Endogenous DPP IV activity was inhibited to reduce degradation of the infused GIP-(1-42), which was infused alone and together with GIP-(3-42), at rates sufficient to mimic postprandial concentrations of each peptide. Glucose, insulin, and glucagon responses were identical irrespective of whether GIP-(1-42) was infused alone or together with GIP-(3-42). We conclude that, although GIP-(3-42) can weakly antagonize cAMP accumulation and insulin output in vitro, it does not behave as a physiological antagonist in vivo.

U2 - 10.1152/ajpendo.00577.2005

DO - 10.1152/ajpendo.00577.2005

M3 - Journal article

C2 - 16608883

VL - 291

SP - E468-75

JO - American Journal of Physiology: Endocrinology and Metabolism

JF - American Journal of Physiology: Endocrinology and Metabolism

SN - 0193-1849

IS - 3

ER -

ID: 8417185