TY - JOUR
T1 - Insulin Signaling in Osteoblasts Integrates Bone Remodeling and Energy Metabolism
AU - Ferron, Mathieu
AU - Wei, Jianwen
AU - Yoshizawa, Tatsuya
AU - Del Fattore, Andrea
AU - DePinho, Ronald A.
AU - Teti, Anna
AU - Ducy, Patricia
AU - Karsenty, Gerard
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - Humdisease
KW - Signaling
UR - http://www.scopus.com/inward/record.url?scp=77955035304&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955035304&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2010.06.003
DO - 10.1016/j.cell.2010.06.003
M3 - Article
C2 - 20655470
AN - SCOPUS:77955035304
VL - 142
SP - 296
EP - 308
JO - Cell
JF - Cell
SN - 0092-8674
IS - 2
ER -