Kainuma Shingo, Tokuda Haruhiko, Fujita Kazuhiko, Kawabata Tetsu, Sakai Go, Matsushima-Nishiwaki Rie, Harada Atsushi, Kozawa Osamu, Otsuka Takanobu
Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan; Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of Clinical Laboratory, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
Biomed Rep. 2016 Dec;5(6):771-775. doi: 10.3892/br.2016.798. Epub 2016 Nov 1.
Incretins, the polypeptide hormone glucose- dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) secreted from the small intestine after nutrient ingestion, are generally known to stimulate insulin secretion from pancreatic β-cells. We previously demonstrated that triiodothyronine (T) stimulates osteocalcin synthesis at least in part through p38 mitogen-activated protein kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effects of GIP and GLP-1 on T-stimulated osteocalcin synthesis and the mechanism of action involved in MC3T3-E1 cells. GIP and GLP-1 markedly suppressed the T-stimulated osteocalcin release. GIP and GLP-1 significantly attenuated the expression levels of osteocalcin mRNA induced by T. The T-stimulated transactivation activity of the thyroid hormone-responsive element was reduced by GIP and GLP-1. These results suggest that incretins repressed the T-stimulated osteocalcin synthesis in osteoblast-like MC3T3-E1 cells, and the suppressive effect of incretins was mediated through transcriptional levels.
肠促胰岛素，即营养物质摄入后从小肠分泌的多肽激素葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽-1（GLP-1），通常被认为可刺激胰腺β细胞分泌胰岛素。我们之前证明，三碘甲状腺原氨酸（T3）至少部分通过成骨细胞样MC3T3-E1细胞中的p38丝裂原活化蛋白激酶刺激骨钙素合成。在本研究中，我们调查了GIP和GLP-1对T3刺激的骨钙素合成的影响以及MC3T3-E1细胞中的作用机制。GIP和GLP-1显著抑制T3刺激的骨钙素释放。GIP和GLP-1显著减弱了T3诱导的骨钙素mRNA的表达水平。GIP和GLP-1降低了T3刺激的甲状腺激素反应元件的反式激活活性。这些结果表明，肠促胰岛素抑制成骨细胞样MC3T3-E1细胞中T3刺激的骨钙素合成，且肠促胰岛素的抑制作用是通过转录水平介导的。
