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Mechanisms of Disease: metabolic effects of growth hormone and insulin-like growth factor 1

Nature Clinical Practice Endocrinology & Metabolism volume 3, pages 302–310 (2007)Cite this article

Abstract

Insulin-like growth factor (IGF) 1 is a member of a family that is involved in growth, development, cell differentiation, and metabolism. IGF1, IGF2 and insulin act primarily through tyrosine-kinase-linked receptors—the IGF1 receptor (IGF1R) and insulin receptor (IR). The IGF1R binds IGF1 and IGF2 with high affinity and the IR binds insulin with high affinity; however, since both receptors share a high degree of structural and functional homology, the IGF1R can bind insulin and the IR can bind the IGFs with reduced affinity. These two receptors can, moreover, form heterodimers, which bind both ligands. Upon binding to the receptors, cascades of tyrosine and serine kinases are stimulated to facilitate growth or metabolism. The IGF2 receptor is a scavenger receptor, and is, therefore, not involved in mediation of growth or metabolic effects of the IGF family and will not be discussed in the current article. IGF1 is a major gene target of growth hormone and its product mediates many of the actions of growth hormone on growth and development; however, IGF1 has actions distinct from those of growth hormone in carbohydrate, lipid, and protein metabolism. For example, excess growth hormone causes insulin resistance and hyperglycemia, whereas IGF1 has insulin-like effects that reduce blood glucose levels and has been used experimentally to treat both type 1 and type 2 diabetes.

Key Points

  • The insulin-like growth factor 1 (IGF1) gene is a major target of growth hormone

  • IGF1 binds the IGF1 receptor (IGF1R) with high affinity and the insulin receptor with low affinity; conversely, insulin can bind IGF1R with lower affinity than it has for the insulin receptor

  • IGF1R and the insulin receptor can form heterodimers that bind both ligands

  • IGF1 has actions distinct from those of growth hormone in carbohydrate, lipid and protein metabolism; IGF1 can reduce blood glucose levels and has been used to treat patients with type 1 and 2 diabetes

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Figure 1: GH actions
Figure 2: The actions of IGF1

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Authors and Affiliations

  1. of the Division of Endocrinology, Department of Medicine, D LeRoith is the Chief, and S Yakar is an Assistant Professor, Diabetes and Bone Diseases, Mount Sinai School of Medicine, New York, NY, USA.,

    Derek LeRoith & Shoshana Yakar

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Correspondence to Derek LeRoith.

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LeRoith, D., Yakar, S. Mechanisms of Disease: metabolic effects of growth hormone and insulin-like growth factor 1. Nat Rev Endocrinol 3, 302–310 (2007). https://doi.org/10.1038/ncpendmet0427

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