Dose-dependent efficacy of the glucose-dependent insulinotropic polypeptide (GIP)receptor antagonistGIP(3-30)NH2 on GIP actions in humans
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Dose-dependent efficacy of the glucose-dependent insulinotropic polypeptide (GIP)receptor antagonistGIP(3-30)NH2 on GIP actions in humans. / Gasbjerg, Laerke Smidt; Bari, Emilie J.; Stensen, Signe; Hoe, Bjorn; Lanng, Amalie R.; Mathiesen, David S.; Christensen, Mikkel B.; Hartmann, Bolette; Holst, Jens J.; Rosenkilde, Mette M.; Knop, Filip Krag.
I: Diabetes, Obesity and Metabolism, Bind 23, Nr. 1, 2021, s. 68-74.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Dose-dependent efficacy of the glucose-dependent insulinotropic polypeptide (GIP)receptor antagonistGIP(3-30)NH2 on GIP actions in humans
AU - Gasbjerg, Laerke Smidt
AU - Bari, Emilie J.
AU - Stensen, Signe
AU - Hoe, Bjorn
AU - Lanng, Amalie R.
AU - Mathiesen, David S.
AU - Christensen, Mikkel B.
AU - Hartmann, Bolette
AU - Holst, Jens J.
AU - Rosenkilde, Mette M.
AU - Knop, Filip Krag
PY - 2021
Y1 - 2021
N2 - The glucose-dependent insulinotropic polypeptide (GIP) fragment GIP(3-30)NH(2)is a selective, competitive GIP receptor antagonist, and doses of 800 to 1200 pmol/kg/min inhibit GIP-induced potentiation of glucose-stimulated insulin secretion by >80% in humans. We evaluated the effects of GIP(3-30)NH(2)across a wider dose range in eight healthy men undergoing six separate and randomized 10-mmol/L hyperglycaemic clamps (A-F) with concomitant intravenous infusion of GIP (1.5 pmol/kg/min; A-E) or saline (F). Clamps A to E involved double-blinded, infusions of saline (A) and GIP(3-30)NH(2)at four rates: 2 (B), 20 (C), 200 (D) and 2000 pmol/kg/min (E), respectively. Mean plasma concentrations of glucose (A-F) and GIP (A-E) were similar. GIP-induced potentiation of glucose-stimulated insulin secretion was reduced by 44 +/- 10% and 84 +/- 10% during clamps D and E, respectively. Correspondingly, the amounts of glucose required to maintain the clamp during D and E were not different from F. GIP-induced suppression of bone resorption and increase in heart rate were lowered by clamps D and E. In conclusion, GIP(3-30)NH(2)provides extensive, dose-dependent inhibition of the GIP receptor in humans, with most pronounced effects of the doses 200 to 2000 pmol/kg/min within the tested range.
AB - The glucose-dependent insulinotropic polypeptide (GIP) fragment GIP(3-30)NH(2)is a selective, competitive GIP receptor antagonist, and doses of 800 to 1200 pmol/kg/min inhibit GIP-induced potentiation of glucose-stimulated insulin secretion by >80% in humans. We evaluated the effects of GIP(3-30)NH(2)across a wider dose range in eight healthy men undergoing six separate and randomized 10-mmol/L hyperglycaemic clamps (A-F) with concomitant intravenous infusion of GIP (1.5 pmol/kg/min; A-E) or saline (F). Clamps A to E involved double-blinded, infusions of saline (A) and GIP(3-30)NH(2)at four rates: 2 (B), 20 (C), 200 (D) and 2000 pmol/kg/min (E), respectively. Mean plasma concentrations of glucose (A-F) and GIP (A-E) were similar. GIP-induced potentiation of glucose-stimulated insulin secretion was reduced by 44 +/- 10% and 84 +/- 10% during clamps D and E, respectively. Correspondingly, the amounts of glucose required to maintain the clamp during D and E were not different from F. GIP-induced suppression of bone resorption and increase in heart rate were lowered by clamps D and E. In conclusion, GIP(3-30)NH(2)provides extensive, dose-dependent inhibition of the GIP receptor in humans, with most pronounced effects of the doses 200 to 2000 pmol/kg/min within the tested range.
KW - dose-response relationship
KW - GIP
KW - GIP receptor antagonist
KW - incretin therapy
KW - pharmacodynamics
KW - GASTRIC-INHIBITORY POLYPEPTIDE
KW - GIP RECEPTOR
KW - GIP(3-30)NH2
KW - ANTAGONIST
U2 - 10.1111/dom.14186
DO - 10.1111/dom.14186
M3 - Journal article
C2 - 32886401
VL - 23
SP - 68
EP - 74
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 1
ER -
ID: 249862811