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Dose‐dependent efficacy of the glucose‐dependent insulinotropic polypeptide ( GIP) receptor antagonist GIP (3‐30) NH 2 on GIP actions in humans
Author(s) -
Gasbjerg Lærke Smidt,
Bari Emilie J.,
Stensen Signe,
Hoe Bjørn,
Lanng Amalie R.,
Mathiesen David S.,
Christensen Mikkel B.,
Hartmann Bolette,
Holst Jens J.,
Rosenkilde Mette M.,
Knop Filip Krag
Publication year - 2021
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.14186
Subject(s) - gastric inhibitory polypeptide , medicine , endocrinology , antagonist , receptor , receptor antagonist , chemistry , insulin , saline , glucose clamp technique , long term potentiation , pancreatic hormone , insulin resistance , glucagon
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.