Recently, it emerged that bone is an important endocrine organ that regulates energy metabolism through osteocalcin, a hormone that favours insulin secretion and sensitivity, and energy expenditure. According to the general rules of endocrinology, these observations suggested that insulin might in turn affect the endocrine function of bones. To address this issue, Ferron et al. engineered an osteoblast-specific insulin-receptor-deficient mouse model and demonstrated that maintenance of whole-body glucose homeostasis requires insulin signalling in osteoblasts. Insulin signalling in osteoblasts essentially hijacks the functional interaction that exists in bone between osteoblasts and osteoclasts. In osteoblasts, insulin signalling inhibits the expression of an inhibitor of bone resorption, thereby upregulating this function. Osteoclasts resorb bone under highly acidic conditions, providing a favourable environment for the activation of osteocalcin, which, in turn, stimulates insulin secretion. This mechanism occurs in mice and in humans. These results further underscore the tight relationship that has emerged recently between bone physiology and glucose homeostasis; they also have important implications for the treatment of diseases such as type 2 diabetes and osteoporosis.

Ferron
M
,
Wei
J
,
Yoshizawa
T
,
Del Fattore
A
,
DePinho
RA
,
Teti
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,
Ducy
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2010
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Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism
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2010