Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation after food ingestion.
Calcium plays a fundamental role as second messenger in intracellular signaling and bone serves as the body's calcium reserve to tightly maintain blood calcium levels. Calcium in ingested meal is the main supply and inadequate calcium intake causes osteoporosis and bone fracture. Here, we describe a novel mechanism of how ingested calcium is deposited on bone. Meal ingestion elicits secretion of the gut hormone gastric inhibitory polypeptide (GIP) from endocrine K cells in the duodenum. Bone histomorphometrical analyses revealed that bone formation parameters in the mice lacking GIP receptor (GIPR(-/-)) were significantly lower than those of wild-type (GIPR(+/+)) mice, and that the number of osteoclasts, especially multinuclear osteoclasts, was significantly increased in GIPR(-/-) mice, indicating that GIPR(-/-) mice have high-turnover osteoporosis. In vitro examination showed the percentage of osteoblastic cells undergoing apoptosis to be significantly decreased in the presence of GIP. Because GIPR(-/-) mice exhibited an increased plasma calcium concentration after meal ingestion, GIP directly links calcium contained in meal to calcium deposition on bone.
Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
Katsushi
K
Tsukiyama
Yuichiro
Y
Yamada
Chizumi
C
Yamada
Norio
N
Harada
Yukiko
Y
Kawasaki
Masahito
M
Ogura
Kazuhisa
K
Bessho
Minqi
M
Li
Norio
N
Amizuka
Masahiro
M
Sato
Nobuyuki
N
Udagawa
Naoyuki
N
Takahashi
Kiyoshi
K
Tanaka
Yutaka
Y
Oiso
Yutaka
Y
Seino
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001862:Bone Resorption / Q000151:congenital; D002118:Calcium / Q000097:blood / Q000378:metabolism; D004435:Eating / Q000502:physiology*; D005749:Gastric Inhibitory Polypeptide / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D010024:Osteoporosis / Q000473:pathology; D015398:Signal Transduction; D013977:Tibia / Q000033:anatomy & histology / Q000254:growth & development
D051017:Apoptosis Regulatory Proteins; D005749:Gastric Inhibitory Polypeptide; D002118:Calcium