[Involvement of insulin and IGF-1 signaling molecules in bone metabolism].

Insulin and IGF-1 signaling is the most important factors in diabetes, but is also important regulators in bone metabolism. Insulin and IGF-1 have anabolic effects on osteoblasts in vitro and an association of diabetes with abnormal bone metabolism has been reported. Insulin receptor substrates (IRS), which is a main target molecule of insulin/IGF-1 receptor signaling, have been shown to play important roles in maintaining normal bone turn-over by skeletal analysis of IRS-1 and -2 knock-out mice. Skeletal analysis of disruptive AKT, a downstream molecule of IRS, in mice also revealed that AKT was established as a crucial regulator of osteoblasts and osteoclasts by promoting their differentiation and survival to maintain bone mass and turnover. Further analysis of molecular network in diabetes and bone metabolism will provide a basis for rational therapeutic targets for bone disorders.