TY - JOUR
T1 - The antiresorptive effect of GIP, but not GLP-2, is preserved in patients with hypoparathyroidism - a randomized crossover study
AU - Skov-Jeppesen, Kirsa
AU - Hepp, Nicola
AU - Oeke, Jannika
AU - Hansen, Morten Steen
AU - Jafari, Abbas
AU - Svane, Maria Saur
AU - Balenga, Nariman
AU - Olson, John A
AU - Frost, Morten
AU - Kassem, Moustapha
AU - Madsbad, Sten
AU - Beck Jensen, Jens-Erik
AU - Holst, Jens Juul
AU - Rosenkilde, Mette Marie
AU - Hartmann, Bolette
N1 - This article is protected by copyright. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are gut hormones secreted postprandially. In healthy humans, both hormones decrease bone resorption accompanied by a rapid reduction in parathyroid hormone (PTH). The aim of this study was to investigate whether the changes in bone turnover after meal intake and after GIP- and GLP-2 injections, respectively, are mediated via a reduction in PTH secretion. This was tested in female patients with hypoparathyroidism given a standardized liquid mixed-meal test (n = 7) followed by a peptide injection-test (n = 4) using a randomized crossover design. We observed that the meal- and GIP-, but not the GLP-2-induced changes in bone turnover markers, were preserved in the patients with hypoparathyroidism. To understand the underlying mechanisms, we examined the expression of the GIP receptor (GIPR) and the GLP-2 receptor (GLP-2R) in human osteoblasts and osteoclasts as well as in parathyroid tissue. The GIPR was expressed in both human osteoclasts and osteoblasts, whereas the GLP-2R was absent or only weakly expressed in osteoclasts. Furthermore, both GIPR and GLP-2R were expressed in parathyroid tissue. Our findings suggest that the GIP-induced effect on bone turnover may be mediated directly via GIPR expressed in osteoblasts and osteoclasts and that this may occur independent of PTH. In contrast, the effect of GLP-2 on bone turnover seems to depend on changes in PTH and may be mediated through GLP-2R in the parathyroid gland.
AB - Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are gut hormones secreted postprandially. In healthy humans, both hormones decrease bone resorption accompanied by a rapid reduction in parathyroid hormone (PTH). The aim of this study was to investigate whether the changes in bone turnover after meal intake and after GIP- and GLP-2 injections, respectively, are mediated via a reduction in PTH secretion. This was tested in female patients with hypoparathyroidism given a standardized liquid mixed-meal test (n = 7) followed by a peptide injection-test (n = 4) using a randomized crossover design. We observed that the meal- and GIP-, but not the GLP-2-induced changes in bone turnover markers, were preserved in the patients with hypoparathyroidism. To understand the underlying mechanisms, we examined the expression of the GIP receptor (GIPR) and the GLP-2 receptor (GLP-2R) in human osteoblasts and osteoclasts as well as in parathyroid tissue. The GIPR was expressed in both human osteoclasts and osteoblasts, whereas the GLP-2R was absent or only weakly expressed in osteoclasts. Furthermore, both GIPR and GLP-2R were expressed in parathyroid tissue. Our findings suggest that the GIP-induced effect on bone turnover may be mediated directly via GIPR expressed in osteoblasts and osteoclasts and that this may occur independent of PTH. In contrast, the effect of GLP-2 on bone turnover seems to depend on changes in PTH and may be mediated through GLP-2R in the parathyroid gland.
U2 - 10.1002/jbmr.4308
DO - 10.1002/jbmr.4308
M3 - Journal article
C2 - 33852173
VL - 36
SP - 1448
EP - 1458
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 8
ER -