CHANGES IN INSULIN-LIKE GROWTH-FACTOR (IGF)-BINDING PROTEINS AFTER IGF-I INJECTIONS IN NONINSULIN-DEPENDENT DIABETICS

Insulin-like growth factor-I (IGF-I) exerts insulin-like effects on fuel metabolism and suppresses insulin secretion in normal subjects. Unlike insulin, circulating IGF-I is bound to high affinity binding proteins (IGFBPs), which modulate IGF action. We have previously shown that IGF-I administration increases IGFBP-1 and -2 and reduces IGFBP-3 in normal subjects. To determine whether similar effects could be demonstrated in an insulin-resistant state, we administered recombinant human IGF-I for 4 days by sc injection to six obese type II diabetics and determined the effects on fasting concentrations of glucose, C-peptide, IGF-I, and IGFBPs. The changes that occurred in glucose C-peptide and IGFBP levels during oral glucose tolerance testing were also quantified. There was no significant decrease in the mean fasting serum glucose or C-peptide level despite a 7-fold increase in mean fasting IGF-I concentrations (P < 0.01). As expected, during oral glucose tolerance testing, the area under the curve of C-peptide was suppressed after an injection of IGF-I (P < 0.05), but the area under the glucose curve did not change significantly. Mean fasting daily IGFBP-1 and -2 rose 2-fold (P < 0.05) and 1.9-fold (P < 0.05), respectively, whereas IGFBP-3 fell by 16% (P < 0.01) after 4 days of injections. IGFBP-1 was suppressed by 32% after oral glucose alone, whereas an injection of IGF-I plus oral glucose were associated with a more marked fall of 53% (despite suppression of C-peptide). In contrast, mean IGFBP-2 concentrations rose by 40% (P < 0.05) after IGF-I and oral glucose, but there was no change in response to oral glucose alone. These changes in IGFBP-1, -2, and -3 could alter the distribution of IGF-I among the various IGFBPs in the circulation. They may also prove to be a marker of metabolic responsiveness to IGF-I. In a substrate-sufficient state, e.g. after oral glucose, IGFBP-1 and -2 show opposite acute responses to IGF-I, and IGF-I has an apparent acute insulin-like effect on IGFBP-1 concentrations that differs from its longer term effect.