Effects of glucose-dependent insulinotropic peptide on osteoclast function

Qing Zhong, Takashi Itokawa, Supriya Sridhar, Kehong Ding, Ding Xie, Baolin Kang, Wendy B Bollag, Roni Jacob Bollag, Mark W Hamrick, Karl Insogna, Carlos M Isales

Research output: Contribution to journalArticlepeer-review

158 Scopus citations


Acute nutrient ingestion leads to a rapid inhibition of bone resorption while effects on makers of bone formation are less marked or absent, suggesting that there is a transient shift toward skeletal accretion in the immediate postprandial period. The cellular bases for these effects are not clear. Glucose-dependent insulinotropic peptide (GIP), a known modulator of glucose-induced insulin secretion, is secreted from intestinal endocrine cells in response to nutrient ingestion. In addition to the effect of GIP on pancreatic β-cells, GIP receptors are expressed by osteoblastic cells in bone, suggesting a role for this incretin hormone in bone formation. To determine whether GIP also plays a role in the anti-resorptive effect of nutrient ingestion, osteoclasts were analyzed for the presence of GIP receptors by PCR, immunohistochemical and immunocytochemical analyses of bone tissue, and freshly isolated mature osteoclasts and osteoclast-like cells cultured in vitro. Osteoclast function was assessed by fetal long bone resorption assay and by use of the Osteologic disc assay. Our results demonstrate that GIP receptor transcripts and protein are present in osteoclasts. In addition, with the use of an in vitro organ culture system and mature osteoclasts, GIP was found to inhibit bone resorption in the organ culture system and the resorptive activity of mature osteoclasts. These data are consistent with the hypothesis that GIP inhibits bone breakdown through a direct effect on osteoclast-resorptive activity and suggest one mechanism for the postprandial reduction in markers of bone breakdown.

Original languageEnglish (US)
Pages (from-to)E543-E548
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number2
StatePublished - Feb 2007


  • Bone breakdown
  • Incretin
  • Nutrition

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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