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, Jr., Jason K. Kim, Klaus H. Kaestner, Gerard Karsenty

Research output: Contribution to journalArticle

175 Citations (Scopus)

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
StatePublished - Dec 29 2008

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Osteocalcin
Leptin
Hyperinsulinism
Insulin
Osteoblasts
Glucose Intolerance
Sympathetic Nervous System
Skeleton
Homeostasis
Fats
Glucose
Genes

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

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

The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity. / Hinoi, Eiichi; Gao, Nan; Jung, Dae Young; Yadav, Vijay; Yoshizawa, Tatsuya; Myers, Martin G.; Chua, Jr., Streamson C.; Kim, Jason K.; Kaestner, Klaus H.; Karsenty, Gerard.

In: Journal of Cell Biology, Vol. 183, No. 7, 29.12.2008, p. 1235-1242.

Research output: Contribution to journalArticle

Hinoi, E, Gao, N, Jung, DY, Yadav, V, Yoshizawa, T, Myers, MG, Chua, Jr., SC, Kim, JK, Kaestner, KH & Karsenty, G 2008, 'The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity', Journal of Cell Biology, vol. 183, no. 7, pp. 1235-1242. https://doi.org/10.1083/jcb.200809113
Hinoi, Eiichi ; Gao, Nan ; Jung, Dae Young ; Yadav, Vijay ; Yoshizawa, Tatsuya ; Myers, Martin G. ; Chua, Jr., Streamson C. ; Kim, Jason K. ; Kaestner, Klaus H. ; Karsenty, Gerard. / The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity. In: Journal of Cell Biology. 2008 ; Vol. 183, No. 7. pp. 1235-1242.
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