The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity

Eiichi Hinoi, Nan Gao, Dae Young Jung, Vijay Yadav, Tatsuya Yoshizawa, Martin G. Myers, Streamson C. Chua, Jason K. Kim, Klaus H. Kaestner, Gerard Karsenty

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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 fulfi ll this function. Remarkably, for our purpose, an osteoblastspecifi c ablation of sympathetic signaling results in a leptindependent hyperinsulinemia. In osteoblasts, 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.

Original languageEnglish (US)
Pages (from-to)1235-1242
Number of pages8
JournalJournal of Cell Biology
Volume183
Issue number7
DOIs
Publication statusPublished - Dec 29 2008

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Hinoi, E., Gao, N., Jung, D. Y., Yadav, V., Yoshizawa, T., Myers, M. G., ... Karsenty, G. (2008). The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity. Journal of Cell Biology, 183(7), 1235-1242. https://doi.org/10.1083/jcb.200809113