GIP's effect on bone metabolism is reduced by the selective GIP receptor antagonist GIP(3-30)NH2
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GIP's effect on bone metabolism is reduced by the selective GIP receptor antagonist GIP(3-30)NH2. / Gasbjerg, Laerke S.; Hartmann, Bolette; Christensen, Mikkel B.; Lanng, Amalie R.; Vilsbøll, Tina; Jorgensen, Niklas R.; Holst, Jens J.; Rosenkilde, Mette M.; Knop, Filip K.
In: Bone, Vol. 130, 115079 , 2020.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - GIP's effect on bone metabolism is reduced by the selective GIP receptor antagonist GIP(3-30)NH2
AU - Gasbjerg, Laerke S.
AU - Hartmann, Bolette
AU - Christensen, Mikkel B.
AU - Lanng, Amalie R.
AU - Vilsbøll, Tina
AU - Jorgensen, Niklas R.
AU - Holst, Jens J.
AU - Rosenkilde, Mette M.
AU - Knop, Filip K.
PY - 2020
Y1 - 2020
N2 - Infusion of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) suppresses the bone resorption marker carboxy-terminal type 1 collagen crosslinks (CTX). Using separate and combined infusions of the selective GIP receptor (GIPR) antagonist, GIP(3-30)NH2, and GIP, we investigated how GIPR inhibition affects bone turnover markers. Ten healthy men (median age 22.5 years (range 21-25), BMI 21.3 kg/m(2) (19.9-24.7)) participated in a randomized, doubled blinded, placebo-controlled, crossover study with four 1 h 12 mmol/l-hyperglycemic clamps on four separate study days with concomitant infusions of GIP, GIP + GIP(3-30)NH2, GIP(3-30)NH2, and placebo, respectively, separated by a period of at least one week. GIP was infused at 1.5 pmol/kg/min and GIP(3-30)NH2 at 800 pmol/kg/min. Plasma glucose was clamped at 12.0 +/- 1.2 mmol/l and plasma levels of GIP and GIP(3-30)NH2 amounted to similar to 80 pmol/l and similar to 50 nmol/l, respectively. GIP suppressed CTX more than placebo (baseline-subtracted AUC - 6,811 +/- 1,260 vs. - 3,012 +/- 3,018 ng/I x min, P = 0.002) and resulted in CTX values of 53 +/- 6.9% (GIP) versus 81 +/- 10% of baseline (placebo), respectively (P = 0.0006), at the end of the hyperglycemic clamp. Co-infusion of GIP and GIP(3-30)NH2 attenuated the GIP-induced CTX suppression by 51 +/- 33% (P = 0.01). The peak value of the bone formation marker N-terminal propeptide of type 1 procollagen (P1NP) peaked at higher levels during GIP (109 +/- 6.7% of baseline) than during GIP(3-30)NH2 infusion (101 +/- 8.9%) (P = 0.049) and GIP suppressed PTH levels compared to GIP(3-30)NH2 alone (P = 0.0158). In conclusion, blockade of the GIPR with GIP(3-30)NH2 diminished GIP-induced CTX and P1NP responses, showing that these effects are GIPR-mediated and that GIPR antagonism might interfere with bone resorption
AB - Infusion of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) suppresses the bone resorption marker carboxy-terminal type 1 collagen crosslinks (CTX). Using separate and combined infusions of the selective GIP receptor (GIPR) antagonist, GIP(3-30)NH2, and GIP, we investigated how GIPR inhibition affects bone turnover markers. Ten healthy men (median age 22.5 years (range 21-25), BMI 21.3 kg/m(2) (19.9-24.7)) participated in a randomized, doubled blinded, placebo-controlled, crossover study with four 1 h 12 mmol/l-hyperglycemic clamps on four separate study days with concomitant infusions of GIP, GIP + GIP(3-30)NH2, GIP(3-30)NH2, and placebo, respectively, separated by a period of at least one week. GIP was infused at 1.5 pmol/kg/min and GIP(3-30)NH2 at 800 pmol/kg/min. Plasma glucose was clamped at 12.0 +/- 1.2 mmol/l and plasma levels of GIP and GIP(3-30)NH2 amounted to similar to 80 pmol/l and similar to 50 nmol/l, respectively. GIP suppressed CTX more than placebo (baseline-subtracted AUC - 6,811 +/- 1,260 vs. - 3,012 +/- 3,018 ng/I x min, P = 0.002) and resulted in CTX values of 53 +/- 6.9% (GIP) versus 81 +/- 10% of baseline (placebo), respectively (P = 0.0006), at the end of the hyperglycemic clamp. Co-infusion of GIP and GIP(3-30)NH2 attenuated the GIP-induced CTX suppression by 51 +/- 33% (P = 0.01). The peak value of the bone formation marker N-terminal propeptide of type 1 procollagen (P1NP) peaked at higher levels during GIP (109 +/- 6.7% of baseline) than during GIP(3-30)NH2 infusion (101 +/- 8.9%) (P = 0.049) and GIP suppressed PTH levels compared to GIP(3-30)NH2 alone (P = 0.0158). In conclusion, blockade of the GIPR with GIP(3-30)NH2 diminished GIP-induced CTX and P1NP responses, showing that these effects are GIPR-mediated and that GIPR antagonism might interfere with bone resorption
KW - Glucose-dependent insulinotropic polypeptide
KW - Glucose-dependent insulinotropic polypeptide receptor antagonist
KW - Gut-bone axis
U2 - 10.1016/j.bone.2019.115079
DO - 10.1016/j.bone.2019.115079
M3 - Journal article
C2 - 31622777
VL - 130
JO - Bone
JF - Bone
SN - 8756-3282
M1 - 115079
ER -
ID: 233585648