INTRAVENOUSLY INJECTED INSULIN-LIKE GROWTH-FACTOR (IGF) I IGF BINDINGPROTEIN-3 COMPLEX EXERTS INSULIN-LIKE EFFECTS IN HYPOPHYSECTOMIZED, BUT NOT IN NORMAL RATS/

Insulin-like growth factor (IGF) circulates in blood in two large mole cular mass forms of 150 and 40 kD. Under normal conditions, most of th e IGF is bound to the 150-kD complex by which it is retained in the ci rculation and therefore unable to exert acute insulin-like actions. Th e aim of this study was to answer the question whether or not IGF in t he 40-kD complex is bioavailable to insulin target tissues and thus ca n cause acute insulin-like effects in vivo. Intravenously injected 1:1 molar recombinant human (rh) IGF I/rhIGF binding protein (BP)-3 compl ex lowered blood glucose and stimulated glycogen synthesis in diaphrag m of hypophysectomized, but not of normal rats. The serum half-lives o f the two components of the complex were similar to each other, but co nsiderably shorter in hyper than in normal rats. On neutral gel filtra tion of serum both components of the injected complex appeared predomi nantly in the 150-kD region in normal rats. In hypox rats which lack t he 150-kD complex they were found in the 40-kD region and disappeared rapidly from the circulation. We conclude that in the absence of the 1 50-kD complex, IGF associated with the 40-kD complex can rapidly leave the vascular compartment, reach insulin or type 1 IGF receptors and e xert acute insulin-like effects.