Effects of the novel (Pro(3))GIP antagonist and exendin(9-39)amide on GIP- and GLP-1-induced cyclic AMP generation, insulin secretion and postprandial insulin release in obese diabetic (ob/ob) mice: evidence that GIP is the major physiological incretin

Victor Gault, Finbarr O'Harte, P Harriott, MH Mooney, BD Green, Peter Flatt

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Abstract

Aims/hypothesis. This study examined the biological effects of the GIP receptor antagonist, (Pro(3))GIP and the GLP-1 receptor antagonist, exendin(9-39)amide. Methods Cyclic AMP production was assessed in Chinese hamster lung fibroblasts transfected with human GIP or GLP-1 receptors, respectively. In vitro insulin release studies were assessed in BRIN-BD11 cells while in vivo insulinotropic and glycaemic responses were measured in obese diabetic (ob/ob) mice. Results. In GIP receptor-transfected fibroblasts, (Pro(3))-GIP or exendin(9-39)amide inhibited GIP-stimulated cyclic AMP production with maximal inhibition of 70.0+/-3.5% and 73.5+/-3.2% at 10(-6) mol/l, respectively. In GLP-1 receptor-transfected fibroblasts, exendin-(9-39)amide inhibited GLP-1-stimulated cyclic AMP production with maximal inhibition of 60+/-0.7% at 10(-6) Mol/l, whereas (Pro(3))GIP had no effect. (Pro(3))GIP specifically inhibited GIP-stimulated insulin release (86%;p
LanguageEnglish
Pages222-230
JournalDiabetologia
Volume46
Issue number2
DOIs
Publication statusPublished - Feb 2003

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Incretins
Glucagon-Like Peptide 1
Cyclic AMP
Insulin
Fibroblasts
Cricetulus
Lung
Pro(3)-glucose-dependent insulinotropic polypeptide
exendin (9-39) amide
Glucagon-Like Peptide-1 Receptor
gastric inhibitory polypeptide receptor

Cite this

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title = "Effects of the novel (Pro(3))GIP antagonist and exendin(9-39)amide on GIP- and GLP-1-induced cyclic AMP generation, insulin secretion and postprandial insulin release in obese diabetic (ob/ob) mice: evidence that GIP is the major physiological incretin",
abstract = "Aims/hypothesis. This study examined the biological effects of the GIP receptor antagonist, (Pro(3))GIP and the GLP-1 receptor antagonist, exendin(9-39)amide. Methods Cyclic AMP production was assessed in Chinese hamster lung fibroblasts transfected with human GIP or GLP-1 receptors, respectively. In vitro insulin release studies were assessed in BRIN-BD11 cells while in vivo insulinotropic and glycaemic responses were measured in obese diabetic (ob/ob) mice. Results. In GIP receptor-transfected fibroblasts, (Pro(3))-GIP or exendin(9-39)amide inhibited GIP-stimulated cyclic AMP production with maximal inhibition of 70.0+/-3.5{\%} and 73.5+/-3.2{\%} at 10(-6) mol/l, respectively. In GLP-1 receptor-transfected fibroblasts, exendin-(9-39)amide inhibited GLP-1-stimulated cyclic AMP production with maximal inhibition of 60+/-0.7{\%} at 10(-6) Mol/l, whereas (Pro(3))GIP had no effect. (Pro(3))GIP specifically inhibited GIP-stimulated insulin release (86{\%};p",
author = "Victor Gault and Finbarr O'Harte and P Harriott and MH Mooney and BD Green and Peter Flatt",
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journal = "Diabetologia",
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T1 - Effects of the novel (Pro(3))GIP antagonist and exendin(9-39)amide on GIP- and GLP-1-induced cyclic AMP generation, insulin secretion and postprandial insulin release in obese diabetic (ob/ob) mice: evidence that GIP is the major physiological incretin

AU - Gault, Victor

AU - O'Harte, Finbarr

AU - Harriott, P

AU - Mooney, MH

AU - Green, BD

AU - Flatt, Peter

PY - 2003/2

Y1 - 2003/2

N2 - Aims/hypothesis. This study examined the biological effects of the GIP receptor antagonist, (Pro(3))GIP and the GLP-1 receptor antagonist, exendin(9-39)amide. Methods Cyclic AMP production was assessed in Chinese hamster lung fibroblasts transfected with human GIP or GLP-1 receptors, respectively. In vitro insulin release studies were assessed in BRIN-BD11 cells while in vivo insulinotropic and glycaemic responses were measured in obese diabetic (ob/ob) mice. Results. In GIP receptor-transfected fibroblasts, (Pro(3))-GIP or exendin(9-39)amide inhibited GIP-stimulated cyclic AMP production with maximal inhibition of 70.0+/-3.5% and 73.5+/-3.2% at 10(-6) mol/l, respectively. In GLP-1 receptor-transfected fibroblasts, exendin-(9-39)amide inhibited GLP-1-stimulated cyclic AMP production with maximal inhibition of 60+/-0.7% at 10(-6) Mol/l, whereas (Pro(3))GIP had no effect. (Pro(3))GIP specifically inhibited GIP-stimulated insulin release (86%;p

AB - Aims/hypothesis. This study examined the biological effects of the GIP receptor antagonist, (Pro(3))GIP and the GLP-1 receptor antagonist, exendin(9-39)amide. Methods Cyclic AMP production was assessed in Chinese hamster lung fibroblasts transfected with human GIP or GLP-1 receptors, respectively. In vitro insulin release studies were assessed in BRIN-BD11 cells while in vivo insulinotropic and glycaemic responses were measured in obese diabetic (ob/ob) mice. Results. In GIP receptor-transfected fibroblasts, (Pro(3))-GIP or exendin(9-39)amide inhibited GIP-stimulated cyclic AMP production with maximal inhibition of 70.0+/-3.5% and 73.5+/-3.2% at 10(-6) mol/l, respectively. In GLP-1 receptor-transfected fibroblasts, exendin-(9-39)amide inhibited GLP-1-stimulated cyclic AMP production with maximal inhibition of 60+/-0.7% at 10(-6) Mol/l, whereas (Pro(3))GIP had no effect. (Pro(3))GIP specifically inhibited GIP-stimulated insulin release (86%;p

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DO - 10.1007/s00125-002-1028-x

M3 - Article

VL - 46

SP - 222

EP - 230

JO - Diabetologia

T2 - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 2

ER -