TY - JOUR
T1 - The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity
AU - Hinoi, Eiichi
AU - Gao, Nan
AU - Jung, Dae Young
AU - Yadav, Vijay
AU - Yoshizawa, Tatsuya
AU - Myers, Martin G.
AU - Chua, Streamson C.
AU - Kim, Jason K.
AU - Kaestner, Klaus H.
AU - Karsenty, Gerard
PY - 2008/12/29
Y1 - 2008/12/29
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.200809113
DO - 10.1083/jcb.200809113
M3 - Article
C2 - 19103808
AN - SCOPUS:59449093033
SN - 0021-9525
VL - 183
SP - 1235
EP - 1242
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 7
ER -