Overview of the IGF-I pathway. IGF-I, IGF-II, insulin, IGF-binding proteins (IGFBPs), IGF-IR, IGF-IIR, and insulin receptor (IR) form a complex pathway. IGF-IR predominantly regulates growth, whereas the IR dominates regulation of metabolism. IGF-IIR (mannose-6-phosphate receptor) regulates IGF-II degradation. IGF-I and IGF-II action is modulated by six IGFBPs. ALS, acid-labile subunit. [Adapted with permission from Lowe WL Jr. Insulin-like growth factors. Sci Med. 1996;3(2):62–71; © 2019 Illustration Presentation ENDOCRINE SOCIETY].