RESPONSE OF INSULIN-LIKE GROWTH-FACTOR (IGF)-BINDING PROTEIN-1 (IGFBP-1) AND ICFBP-3 TO IGF-I TREATMENT IN SEVERE INSULIN-RESISTANCE

It has been suggested that recombinant human IGF-I (rhIGF-I) is a potential therapeutic agent in diabetes mellitus. It is known to have glucose-lowering effects in normal individuals, in patients with non-insulin-dependent diabetes (NIDDM) and in extreme insulin-resistant states. IGF-binding proteins (IGFBPs) have the potential to affect the biological activity of rhIGF-I. We have studied the effect of infused rhIGF-I on IGFBP-1 and IGFBP-3 in a patient with Mendenhall's syndrome, a rare insulin-resistant state. During an infusion of 20 mg rhIGF-I, glucose concentrations fell from 44.1+/-7.2 to 31.5+/-7.2 (S.E.M.) mmol/l (P=0.001), and insulin and C-peptide levels fell from 920+/-62 to 542+/-45 mU/l (P=0.008) and 5466+/-633 to 3071+/-297 pmol/l (P=0.02) respectively. Significant lowering of phosphate, magnesium and alkaline phosphatase concentrations was also noted. IGF-I levels rose from 48+/-10.2 to 410+/-50.1 mu g/l (P=0.001), and those of IGF-II fell from 279.8+/-8.3 to 104.3+/-7.9 mu g/l (P=0.001). IGFBP-1 concentrations did not significantly change during the infusion but those of IGFBP-3 increased from 1655+/-127 to 2197+/-334 mu g/l (P=0.002), despite a significant fall in GH concentrations from 10.7+/-2.6 to 4.1+/-1.1 mU/l (P=0.007), suggesting that IGFBP-3 regulation is also IGF-I-dependent. The lack of response of IGFBP-1 to a significant fall in insulin levels suggests that impaired insulin receptor function alters the usual regulation of IGFBP-1 by insulin. These findings are of importance, given the potential use of rhIGF-1 in NIDDM.