title: Attenuation by incretins of thyroid hormone-stimulated osteocalcin synthesis in osteoblasts.
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 (T3) 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 T3-stimulated osteocalcin synthesis and the mechanism of action involved in MC3T3-E1 cells. GIP and GLP-1 markedly suppressed the T3-stimulated osteocalcin release. GIP and GLP-1 significantly attenuated the expression levels of osteocalcin mRNA induced by T3. The T3-stimulated transactivation activity of the thyroid hormone-responsive element was reduced by GIP and GLP-1. These results suggest that incretins repressed the T3-stimulated osteocalcin synthesis in osteoblast-like MC3T3-E1 cells, and the suppressive effect of incretins was mediated through transcriptional levels.
authors.affiliation: 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.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kainuma
authors.affiliation: 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.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.affiliation: 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.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fujita
authors.affiliation: 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.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kawabata
authors.affiliation: 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.
authors.forename: Go
authors.initials: G
authors.lastname: Sakai
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.affiliation: Department of Orthopedic Surgery, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Harada
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
authors.affiliation: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
keywords: glucagon-like peptide-1; glucose-dependent insulinotropic peptide; incretin; osteoblast; osteocalcin; triiodothyronine