Endocrine actions of osteocalcin. Circulating osteocalcin and particularly its undercarboxylated fraction (released during active bone resorption) exert a direct effect on β cells, stimulating insulin production as well as on adipocytes enhancing adiponectin production. Adiponectin itself is able to promote insulin sensitivity. In turn, insulin also acts directly on osteoblast and indirectly on osteoclast. Osteoclast stimulates bone resorption with subsequent release of undercarboxylated osteocalcin in blood circulation. Finally, osteocalcin has a role also on Leydig cells, increasing their activity and testosterone production.