Type Size

    Insulin Signaling in Osteoblasts Integrates Bone Remodeling and Energy Metabolism

    Cell. 2010 Jul 23;142(2):296-308.

    The authors find alter glucose homeostasis in mice with targeted deletion of the insulin receptor in osteoblasts. They also show that decrboxylation of osteocalcin can occur in the acid environment of the resorption lacuna of the osteoclast, which releases undercarboxylated osteocalcin from bone. They demonstrate that insulin influences bone resorption by regulating osteoprotegerin, an inhibitor of RANKL.

    Authors: Ferron M, Wei J, Yoshizawa T, et. al

    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.

    Full Text