Expression of glucagon-like peptide-1 receptor and glucose‑dependent insulinotropic polypeptide receptor is regulated by the glucose concentration in mouse osteoblastic MC3T3-E1 cells

Int J Mol Med. 2014 Aug;34(2):475-82. doi: 10.3892/ijmm.2014.1787. Epub 2014 May 27.


Glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP‑1R) are incretin receptors that play important roles in regulating insulin secretion from pancreatic β cells. Incretin receptors are also thought to play a potential role in bone metabolism. Osteoblasts in animals and humans express GIPR; however, the presence of GLP-1R in these cells has not been reported to date. Thus, the aim of this study was to determine whether GLP-1R and GIPR are expressed in osteoblastic cells, and whether their expression levels are regulated by the extracellular glucose concentration. Mouse osteoblastic MC3T3-E1 cells were cultured in medium containing normal (5.6 mM) or high (10, 20 or 30 mM) glucose concentrations, with or without bone morphogenetic protein-2 (BMP-2). RT-PCR, western blot analysis and immunofluorescence were carried out to determine GIPR and GLP-1R mRNA and protein expression levels. Cell proliferation was also assessed. The GLP-1R and GIPR mRNA expression levels were higher in the MC3T3-E1 cells cultured in medium containing high glucose concentrations with BMP-2 compared with the cells cultured in medium containing normal glucose concentrations with or without BMP-2. GLP-1R protein expression increased following culture in high-glucose medium with BMP-2 compared with culture under normal glucose conditions. However, the cellular localization of GLP-1R was not affected by either glucose or BMP-2. In conclusion, our data demonstrate that the expression of GLP-1R and GIPR is regulated by glucose concentrations in MC3T3-E1 cells undergoing differentiation induced by BMP-2. Our results reveal the potential role of incretins in bone metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / metabolism
  • Cell Differentiation / genetics
  • Cell Line
  • Gastric Inhibitory Polypeptide
  • Gene Expression Regulation
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide-1 Receptor
  • Glucose / metabolism*
  • Humans
  • Insulin / metabolism*
  • Mice
  • Osteoblasts / metabolism
  • Receptors, Gastrointestinal Hormone / biosynthesis*
  • Receptors, Gastrointestinal Hormone / metabolism
  • Receptors, Glucagon / biosynthesis*
  • Receptors, Glucagon / metabolism


  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • GLP1R protein, human
  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Insulin
  • Receptors, Gastrointestinal Hormone
  • Receptors, Glucagon
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • gastric inhibitory polypeptide receptor
  • Glucose