Skeletal Actions of Insulin

Insulin and the insulin-like growth factors (IGFs) are among the most familiar and widely studied growth factors. These related molecules evolved from a common precursor system comprised of a single receptor and multiple ligands that functioned in lower animals to enable a broad range of physiologic processes, including smell, food consumption, metabolism, growth, reproduction, and dormancy. In higher organisms, including mammals, the insulin and IGF ligands and their receptors evolved more circumscribed functions: IGFs are viewed as central to cell proliferation, survival, and organism growth, and insulin serves primarily in the regulation of fuel accumulation, storage, and energy expenditure. Such a simplistic paradigm, however, overlooks the fact that insulin and IGF-1 continue to exert overlapping roles in several physiologic processes. Indeed, recent studies have identified new skeletal actions of insulin, which suggest that insulin-responsive bone cells participate in the regulation of global energy homeostasis. Such findings raise new questions on the nature of the fuel sensing and processing mechanisms in bone and their relative importance to overall energy homeostasis in mammals. This chapter reviews our current understanding of insulin’s role in bone in the context of these recent findings and identifies key areas where additional work is needed.