Insulin Signaling in Osteoblasts Integrates Bone Remodeling and Energy Metabolism

Mathieu Ferron, Jianwen Wei, Tatsuya Yoshizawa, Andrea Del Fattore, Ronald A. DePinho, Anna Teti, Patricia Ducy, Gerard Karsenty

Research output: Contribution to journalArticlepeer-review


The broad expression of the insulin receptor suggests that the spectrum of insulin function has not been fully described. A cell type expressing this receptor is the osteoblast, a bone-specific cell favoring glucose metabolism through a hormone, osteocalcin, that becomes active once uncarboxylated. We show here that insulin signaling in osteoblasts is necessary for whole-body glucose homeostasis because it increases osteocalcin activity. To achieve this function insulin signaling in osteoblasts takes advantage of the regulation of osteoclastic bone resorption exerted by osteoblasts. Indeed, since bone resorption occurs at a pH acidic enough to decarboxylate proteins, osteoclasts determine the carboxylation status and function of osteocalcin. Accordingly, increasing or decreasing insulin signaling in osteoblasts promotes or hampers glucose metabolism in a bone resorption-dependent manner in mice and humans. Hence, in a feed-forward loop, insulin signals in osteoblasts activate a hormone, osteocalcin, that promotes glucose metabolism.

Original languageEnglish
Pages (from-to)296-308
Number of pages13
Issue number2
Publication statusPublished - Jul 2010


  • Humdisease
  • Signaling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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