Abstract
Osteocalcin is secreted by osteoblasts and improves insulin sensitivity in vivo, although
mechanisms remain unclear. We tested the hypothesis that osteocalcin directly modulates
cell biology in insulin-targeted peripheral tissues. In L-6 myocytes, osteocalcin
stimulated glucose transport both in the absence (basal) and presence of insulin.
Similarly, in primary cultured adipocytes, both carboxylated and uncarboxylated osteocalcin
increased basal and insulin-stimulated glucose transport as well as insulin sensitivity.
Osteocalcin also increased basal and insulin-stimulated glucose oxidation, though
there was no effect on fatty acid synthesis or lipolysis. In primary-cultured adipocytes,
both forms of osteocalcin suppressed secretion of tumor necrosis factor alpha into
the media; however, only carboxylated osteocalcin suppressed interleukin 6 release,
and neither form of osteocalcin modulated monocyte chemoattractant protein-1 secretion.
Both carboxylated and uncarboxylated osteocalcin increased secretion of adiponectin
and the anti-inflammatory cytokine interleukin 10. In conclusion, both carboxylated
and uncarboxylated osteocalcin directly increase glucose transport in adipocytes and
muscle cells, while suppressing proinflammatory cytokine secretion and stimulating
interleukin 10 and adiponectin release. Thus, these results provide a mechanism for
the insulin-sensitizing effects of osteocalcin and help elucidate the role that bone
plays in regulating systemic metabolism.
Key words
glucose homeostasis - metabolism - adipocyte biology
