Abstract

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
Original languageEnglish
Article number115079
JournalBone
Volume130
Number of pages6
ISSN8756-3282
DOIs
Publication statusPublished - 2020

Keywords

  • Glucose-dependent insulinotropic polypeptide
  • Glucose-dependent insulinotropic polypeptide receptor antagonist
  • Gut-bone axis

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