EFFECT OF INSULIN ON THE HEPATIC PRODUCTION OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 (IGFBP-1), IGFBP-3, AND IGF-I IN INSULIN-DEPENDENT DIABETES

Insulin-like growth factors (IGFs) circulate attached to binding prote ins (IGFBPs). Only the unbound form of IGF is suggested to be biologic al active. The main source of circulating IGF-I and IGFBP-1 is conside red to be the liver, but that of circulating IGFBP-3 is not known. IGF -I and IGFBP-3 are GH dependent, whereas IGFBP-1 is insulin regulated. The aim of the present study was to examine the effect of insulin on the hepatic secretion of IGFBP-1, IGFBP-3, and IGF-I. Seven insulin-de pendent diabetic patients in whom insulin was withheld for 12 h were s tudied in the overnight fasted state. Blood was sampled simultaneously from the hepatic vein, a peripheral vein, and an artery before and du ring insulin infusion for 3 h. The basal IGFBP-1 levels in the periphe ral vein were several-fold elevated (249 +/- 44 mu g/ L) compared to t hose in healthy subjects (37 +/- 2 mu g/L). Fasting IGFBP-1 concentrat ions were inversely correlated to the insulin levels (r = -0.918; P < 0.001). The mean IGF-I concentration (175 +/- 17 mu g/L; -1.62 +/- 0.3 8 SD score) was decreased compared with that in age-matched healthy su bjects. The basal IGFBP-3 levels in the peripheral vein (4.50 +/- 0.33 mg/L) were within the normal range. There was a significant correlati on in the hepatic vein between fasting IGF-I and IGFBP-3 levels (r = 0 .928; P < 0.001). Basal splanchnic IGFBP-1 production was 18 +/- 7 mu g/min, whereas no basal net exchanges of IGF-I or IGFBP-3 were observe d across the splanchnic area. Insulin inhibited splanchnic IGFBP-1 pro duction within 120 min and glucose output within 20 min. Serum IGF-I, but not IGFBP-3, concentrations increased significantly during the ins ulin infusion. In summary, this study demonstrates the existence of co nsiderable IGFBP-1 production from the liver during insulinopenia and the complete blocking of splanchnic IGFBP-1 production and increases i n serum levels of IGF-I by insulin despite no effect on IGFBP-3 levels . Thus, insulin may play a role in determining the bioavailability of IGF-I.