The role of endogenous GIP and GLP-1 in postprandial bone homeostasis.

Abstract

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are well known for their insulinotropic effects and they are thought to affect bone homeostasis as mediators in the so-called entero-osseous axis. We examined the contributions of endogenous GIP and GLP-1, respectively, to postprandial bone homeostasis, in healthy subjects in two randomized and double-blind crossover studies. We included healthy men who received either four oral glucose tolerance tests (OGTTs) (n = 18, median age 27 (range 20-70), BMI 27.2 (22.4-37.0) kg/m2) or liquid mixed meal tests (MMTs) (n = 12, age 23 (19-65), BMI 23.7 (20.3-25.5) kg/m2) with infusions of 1) the GIP receptor antagonist GIP(3-30)NH2, 2) the GLP-1 receptor antagonist exendin(9-39)NH2, 3) both GIP(3-30)NH2 and exendin(9-39)NH2, or 4) placebo infusions (saline) on four separate visits. Bone resorption was evaluated from levels of circulating carboxy-terminal collagen crosslinks (CTX) and bone formation from levels of procollagen type 1 amino-terminal propeptide (P1NP). During placebo infusions, baseline-subtracted area under the curve values for CTX were -39 ± 5.0 (OGTT) and -57 ± 4.3 ng/ml × min (MMT). When GIP(3-30)NH2 was administered, CTX suppression was significantly diminished compared to placebo (-30 ± 4.8 (OGTT) and -45 ± 4.6 ng/ml × min (MMT), P = 0.0104 and P = 0.0288, respectively, compared to placebo. During exendin(9-39)NH2 infusion, CTX suppression after OGTT/MMT was similar to placebo (P = 0.28 (OGTT) and P = 0.93 (MMT)). The relative contribution of endogenous GIP to postprandial suppression of bone resorption during both OGTT and MMT was similar and reached 22-25%. There were no differences in P1NP concentrations between interventions. In conclusion, endogenous GIP contributes by up to 25% to postprandial suppression of bone resorption in humans whereas an effect of endogenous GLP-1 could not be demonstrated.

• Authors: Mads M Helsted, Lærke S Gasbjerg, Amalie R Lanng, Natasha C Bergmann, Signe Stensen, Bolette Hartmann, Mikkel B Christensen, Jens J Holst, Tina Vilsbøll, Mette M Rosenkilde, Filip K Knop
• Journal: Bone (Bone) Vol. 140 Pg. 115553 (11 2020) ISSN: 1873-2763 [Electronic] United States
• PMID: 32730920 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Insulin
• Peptide Fragments
• Receptors, Gastrointestinal Hormone
• Gastric Inhibitory Polypeptide
• Glucagon-Like Peptide 1
• gastric inhibitory polypeptide receptor

Topics

• Adult
• Blood Glucose
• Cross-Over Studies
• Double-Blind Method
• Gastric Inhibitory Polypeptide
• Glucagon-Like Peptide 1
• Homeostasis
• Humans
• Insulin
• Male
• Peptide Fragments
• Receptors, Gastrointestinal Hormone
• Young Adult