TY - JOUR
T1 - Glucose-dependent insulinotropic polypeptide receptor knockout mice have altered bone turnover
AU - Xie, Ding
AU - Cheng, Hua
AU - Hamrick, Mark
AU - Zhong, Qing
AU - Ding, Ke Hong
AU - Correa, Daniel
AU - Williams, Sandra
AU - Mulloy, Anthony
AU - Bollag, Wendy
AU - Bollag, Roni J.
AU - Runner, Royce R.
AU - McPherson, James C.
AU - Insogna, Karl
AU - Isales, Carlos M.
PY - 2005/12/1
Y1 - 2005/12/1
N2 - 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.
AB - 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.
KW - GIP
KW - Gastric inhibitory peptide
KW - Hormones
KW - Incretin
KW - Nutrition
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U2 - 10.1016/j.bone.2005.06.021
DO - 10.1016/j.bone.2005.06.021
M3 - Article
C2 - 16219496
AN - SCOPUS:28844478542
VL - 37
SP - 759
EP - 769
JO - Bone
JF - Bone
SN - 8756-3282
IS - 6
ER -