Novel functions for insulin in bone.

The insulin-like growth factors (IGF) evolved in lower animals to enable a wide range of physiologic processes, including smell, food consumption, metabolism, growth, reproduction, and dormancy. These functions were accomplished by the actions of multiple related ligands that activated a common transmembrane receptor protein. In higher organisms, including mammals, the insulin and IGF ligands and their receptors evolved to function in a more circumscribed fashion. The contemporary model assigns IGFs as central regulators of cell proliferation, survival, and organism growth, whereas insulin's action dominates at the level of regulation of fuel accumulation, storage, and energy expenditure. Such a simplistic paradigm, however, obscures the fact that insulin and IGF-1 continue to exert overlapping roles in several physiologic processes. Indeed, recent studies have identified previously unappreciated skeletal actions of insulin, which suggests that insulin-responsive bone cells participate in the regulation of global energy homeostasis. These findings raise intriguing questions on the nature of the fuel sensing and processing mechanisms in bone and their relative importance to overall energy homeostasis in mammals. Answers to these questions should ultimately improve the ability to diagnose and manage patients with metabolic diseases such as diabetes and osteoporosis.