Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Bone. 2012 Feb;50(2):452-6. doi: 10.1016/j.bone.2011.06.018. Epub 2011 Jun 24.
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.
胰岛素样生长因子（IGF）在较低等动物中进化，以实现广泛的生理过程，包括嗅觉、食物摄入、代谢、生长、繁殖和休眠。这些功能是通过多种相关配体的作用来实现的，这些配体激活了一种共同的跨膜受体蛋白。在包括哺乳动物在内的高等生物中，胰岛素和 IGF 配体及其受体进化为以更受限制的方式发挥作用。当前的模型将 IGF 作为细胞增殖、存活和生物体生长的核心调节剂，而胰岛素的作用则主要在调节燃料积累、储存和能量消耗方面。然而，这种过于简单的范式掩盖了一个事实，即胰岛素和 IGF-1 继续在几个生理过程中发挥重叠作用。事实上，最近的研究已经确定了胰岛素在骨骼中以前未被认识到的作用，这表明胰岛素反应性骨细胞参与了全身能量平衡的调节。这些发现提出了有关骨骼中燃料感应和处理机制的性质及其对哺乳动物整体能量平衡的相对重要性的有趣问题。对这些问题的回答最终应该能够提高诊断和治疗糖尿病和骨质疏松症等代谢性疾病患者的能力。
