Glucose-dependent insulinotropic polypeptide receptor knockout mice have altered bone turnover.
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone, which is secreted from endocrine cells in the small intestine after meal ingestion. GIP has been shown to affect osteoblastic function in vitro; however, the in vivo effects of GIP on bone remodeling remain unclear. In the present study, we investigated the role of GIP in modulating bone turnover, by evaluating serum markers of bone turnover, bone density, bone morphology, and changes in biomechanical bone strength over time (one to five months) in GIP receptor knockout mice (GIPR-/- mice). The GIPR-/- mice showed a decreased bone size, lower bone mass, altered bone microarchitecture and biomechanical properties, and altered parameters for bone turnover, especially in bone formation. Moreover, the effects of GIP on bone mass were site-specific and compensatory mechanism developed over time and ameliorated the impact of the loss of GIP signaling on bone mass. Further, GIPR-/- mice had earlier age-related changes than wild-type mice in body composition, including bone mass, lean body mass, and fat percentage. In summary, our results indicate that GIP has an anabolic effect on bone mass and bone quality and suggests that GIP may be a hormonal link between nutrient ingestion and utilization.
Xie
Ding
D
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Department of Medicine, CB-2803, 1120 15th Street, Augusta, GA 30912, USA.
Cheng
Hua
H
Hamrick
Mark
M
Zhong
Qing
Q
Ding
Ke-Hong
KH
Correa
Daniel
D
Williams
Sandra
S
Mulloy
Anthony
A
Bollag
Wendy
W
Bollag
Roni J
RJ
Runner
Royce R
RR
McPherson
James C
JC
Insogna
Karl
K
Isales
Carlos M
CM
D015502:Absorptiometry, Photon; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001835:Body Weight; D015519:Bone Density; D016723:Bone Remodeling; D001842:Bone and Bones / Q000737:chemistry / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D021621:Imaging, Three-Dimensional; D051379:Mice; D018345:Mice, Knockout; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*
D015415:Biomarkers; D011964:Receptors, Gastrointestinal Hormone; C041086:gastric inhibitory polypeptide receptor