Hioki Tomoyuki, Kuroyanagi Gen, Fujita Kazuhiko, Sakai Go, Kawabata Tetsu, Kim Woo, Tachi Junko, Matsushima-Nishiwaki Rie, Iida Hiroki, Kozawa Osamu, Tokuda Haruhiko
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan.
Department of Dermatology, Kizawa Memorial Hospital, Minokamo, Japan.
Horm Metab Res. 2022 Jan;54(1):42-49. doi: 10.1055/a-1713-7967. Epub 2022 Jan 5.
Incretins 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 F (PGF) 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 PGF-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 PGF-induced synthesis of IL-6 in osteoblast-like MC3T3-E1 cells. In addition, GIP and GLP-1 significantly enhanced the PGF-induced mRNA expression levels of IL-6. On the other hand, GIP and GLP-1 markedly stimulated the PGF-induced synthesis of osteoprotegerin. However, the phosphorylation of p44/p42 MAP kinase, p38 MAP kinase, or JNK induced by PGF was not affected by GIP or GLP-1. Therefore, these results strongly suggest that incretins enhance the PGF-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.
肠促胰岛素包括葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽-1（GLP-1），在口服食物后从小肠分泌，目前已知其可刺激胰腺β细胞分泌胰岛素，并用于治疗2型糖尿病。我们之前报道过，前列腺素F（PGF）可刺激成骨样MC3T3-E1细胞中白细胞介素-6（IL-6）和骨保护素的合成，且IL-6和骨保护素的释放是通过p44/p42丝裂原活化蛋白（MAP）激酶、p38 MAP激酶或应激激活蛋白激酶/c-Jun氨基末端激酶（SAPK/JNK）途径介导的。在本研究中，我们研究了包括GLP-1和GIP在内的肠促胰岛素对PGF诱导的IL-6和骨保护素合成的影响，并在成骨样MC3T3-E1细胞中研究了其详细机制。我们发现，GIP和GLP-1显著刺激了PGF诱导的成骨样MC-3T3-E1细胞中IL-6的合成。此外，GIP和GLP-1显著提高了PGF诱导的IL-6的mRNA表达水平。另一方面，GIP和GLP-1显著刺激了PGF诱导的骨保护素的合成。然而，PGF诱导的p44/p42 MAP激酶、p38 MAP激酶或JNK的磷酸化不受GIP或GLP-1的影响。因此，这些结果有力地表明，肠促胰岛素增强了PGF诱导的成骨样MC3T3-E1细胞中IL-6和骨保护素的合成。然而，这些合成不是通过p44/p42 MAP激酶、p38 MAP激酶或JNK途径介导的。
