AbstractIncretins including glucose-dependent insulinotropic polypeptide (GIP) and
glucagon-like peptide-1 (GLP-1), which are secreted from the small intestine
after oral food ingestion, are currently well-known to stimulate insulin
secretion from pancreatic β-cells and used for the treatment of type 2
diabetes mellitus. We have previously reported that prostaglandin
F2α (PGF2α) stimulates the synthesis
of interleukin-6 (IL-6) and osteoprotegerin in osteoblast-like MC3T3-E1 cells,
and that IL-6 and osteoprotegerin release are mediated through the
p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase or
stress-activated protein kinase/c-Jun N-terminal kinase
(SAPK/JNK) pathways. In the present study, we investigated the effects
of incretins including GLP-1 and GIP, on the PGF2α-induced
synthesis of IL-6 and osteoprotegerin and examined the detailed mechanism in
osteoblast-like MC3T3-E1 cells. We found that GIP and GLP-1 significantly
stimulated the PGF2α-induced synthesis of IL-6 in
osteoblast-like MC3T3-E1 cells. In addition, GIP and GLP-1 significantly
enhanced the PGF2α-induced mRNA expression levels of IL-6. On
the other hand, GIP and GLP-1 markedly stimulated the
PGF2α-induced synthesis of osteoprotegerin. However, the
phosphorylation of p44/p42 MAP kinase, p38 MAP kinase, or JNK induced by
PGF2α was not affected by GIP or GLP-1. Therefore, these
results strongly suggest that incretins enhance the
PGF2α-induced synthesis of IL-6 and osteoprotegerin in
osteoblast-like MC3T3-E1 cells. However, these syntheses are not mediated
through p44/p42 MAP kinase, p38 MAP kinase, or JNK pathways.