Abstract
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(3)) 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(3)-stimulated osteocalcin synthesis and the mechanism of action involved in MC3T3-E1 cells. GIP and GLP-1 markedly suppressed the T(3)-stimulated osteocalcin release. GIP and GLP-1 significantly attenuated the expression levels of osteocalcin mRNA induced by T(3). The T(3)-stimulated transactivation activity of the thyroid hormone-responsive element was reduced by GIP and GLP-1. These results suggest that incretins repressed the T(3)-stimulated osteocalcin synthesis in osteoblast-like MC3T3-E1 cells, and the suppressive effect of incretins was mediated through transcriptional levels.