References
Query Results -- Details
MGI Accession ID: MGI:3836495
J Number: J:145998
Other Accession IDs:
Title: The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity.
Authors: Hinoi E; Gao N; Jung DY; Yadav V; Yoshizawa T; Myers MG Jr; Chua SC Jr; Kim JK; Kaestner KH; Karsenty G
Journal: J Cell Biol
Volume: 183
Issue: 7
Date: 2008 Dec 29
Year: 2008
Pages: 1235-42
Review Status: Peer Reviewed
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 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.
Additional Information:
