[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.
Ogata
Naoshi
N
University of Tokyo, Division of Tissue Engineering.
Kawaguchi
Hiroshi
H
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D016723:Bone Remodeling / Q000235:genetics; D001842:Bone and Bones / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C526292:IRS1 protein, human; C526297:IRS2 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526295:Irs1 protein, mouse; C526298:Irs2 protein, mouse; D010750:Phosphoproteins; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases