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. 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.
Ferron
Mathieu
M
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Wei
Jianwen
J
Yoshizawa
Tatsuya
T
Del Fattore
Andrea
A
DePinho
Ronald A
RA
Teti
Anna
A
Ducy
Patricia
P
Karsenty
Gerard
G
D000818:Animals; D016723:Bone Remodeling; D002478:Cells, Cultured; D004734:Energy Metabolism; D005109:Extracellular Matrix; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D015398:Signal Transduction
D007328:Insulin; D015675:Osteocalcin; D005947:Glucose