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- Title
The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity.
- Authors
Hinoi, Eiichi; Gao, Nan; Jung, Dae Young; Yadav, Vijay; Yoshizawa, Tatsuya; Myers Jr., Martin G.; Chua Jr., Streamson C.; Kim, Jason K.; Kaestner, Klaus H.; Karsenty, Gerard
- Abstract
The osteoblast-secreted molecule osteocalcin favors insulin secretion, but how this function is regulated in vivo by extracellular signals is for now unknown. In this study, we show that leptin, which instead inhibits insulin secretion, partly uses the sympathetic nervous system to fulfill this function. Remarkably, for our purpose, an osteoblast-specific ablation of sympathetic signaling results in a leptin-dependent hyperinsulinemia. In osteablasts, sympathetic tone stimulates expression of Esp, a gene inhibiting the activity of osteocalcin, which is an insulin secretagogue. Accordingly, Esp inactivation doubles hyperinsulinemia and delays glucose intolerance in ob/ob mice, whereas Osteocalcin inactivation halves their hyperinsulinemia. By showing that leptin inhibits insulin secretion by decreasing osteocalcin bioactivity, this study illustrates the importance of the relationship existing between fat and skeleton for the regulation of glucose homeostasis.
- Subjects
LEPTIN; INSULIN; SYMPATHETIC nervous system; GENES; GLUCOSE; HOMEOSTASIS
- Publication
Journal of Cell Biology, 2008, Vol 183, Issue 7, p1235
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200809113