Insulin Signaling in Osteoblasts Integrates Bone Remodeling and Energy Metabolism

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....

Full description

Saved in:
Bibliographic Details
Published inCell Vol. 142; no. 2; pp. 296 - 308
Main Authors Ferron, Mathieu, Wei, Jianwen, Yoshizawa, Tatsuya, Del Fattore, Andrea, DePinho, Ronald A., Teti, Anna, Ducy, Patricia, Karsenty, Gerard
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 23.07.2010
Subjects
Animals
Bone Remodeling
Cells, Cultured
Energy Metabolism
Extracellular Matrix
Glucose - metabolism
Humans
HUMDISEASE
Insulin - metabolism
Mice
Mice, Inbred C57BL
Osteoblasts - metabolism
Osteocalcin - metabolism
Signal Transduction
SIGNALING
HUMDISEASE
SIGNALING
Online AccessGet full text

Cover

More Information
Summary: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. [Display omitted] ▸ Insulin signaling in mouse osteoblasts increases activity of the hormone osteocalcin ▸ Osteocalcin activation depends on the acidic pH in the bone resorption area ▸ Enhanced osteocalcin activity promotes glucose metabolism via bone resorption ▸ Regulation of glucose metabolism by bone also occurs in humans
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
These authors contributed equally and were placed in alphabetical order
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2010.06.003