Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation after food ingestion
Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation after food ingestion
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DOI：
10.1210/me.2005-0187
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发表时间：
2006-07-01
影响因子：
--
通讯作者：
Seino, Yutaka
中科院分区：
文献类型：
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作者：
Tsukiyama, Katsushi;Yamada, Yuichiro;Seino, Yutaka
钙在细胞内信号传导中作为第二信使发挥着重要作用，骨作为身体的钙储备，以紧密维持血钙水平。膳食中的钙是人体钙的主要来源，钙摄入不足会引起骨质疏松和骨折。在这里，我们描述了一种新的机制，摄入的钙是如何沉积在骨骼上。摄食促进十二指肠内分泌K细胞分泌胃肠激素胃抑制多肽（GIP）。骨组织形态计量学分析显示，GIP受体缺失小鼠（GIPR（-/-））的骨形成参数显著低于野生型（GIPR（+/+））小鼠，而破骨细胞，尤其是多核破骨细胞数量在GIPR（-/-）小鼠中显著增加，表明GIPR（-/-）小鼠具有高转换性骨质疏松。体外实验表明，GIP的存在显著降低了成骨细胞凋亡的百分比。因为GIPR（-/-）小鼠在进食后表现出增加的血浆钙浓度，所以GIP直接将膳食中所含的钙与骨上的钙沉积联系起来。
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.