TY - JOUR
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
U2 - 10.1007/s00125-002-1028-x
DO - 10.1007/s00125-002-1028-x
M3 - Article
SN - 1432-0428
VL - 46
SP - 222
EP - 230
JO - Diabetologia
JF - Diabetologia
IS - 2
ER -
