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

J Clin Endocrinol Metab. 1994 Sep;79(3):872-8. doi: 10.1210/jcem.79.3.7521354.


Insulin-like growth factors (IGFs) circulate attached to binding proteins (IGFBPs). Only the unbound form of IGF is suggested to be biological active. The main source of circulating IGF-I and IGFBP-1 is considered 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-dependent diabetic patients in whom insulin was withheld for 12 h were studied in the overnight fasted state. Blood was sampled simultaneously from the hepatic vein, a peripheral vein, and an artery before and during insulin infusion for 3 h. The basal IGFBP-1 levels in the peripheral vein were several-fold elevated (249 +/- 44 micrograms/L) compared to those in healthy subjects (37 +/- 2 micrograms/L). Fasting IGFBP-1 concentrations were inversely correlated to the insulin levels (r = -0.918; P < 0.001). The mean IGF-I concentration (175 +/- 17 micrograms/L; -1.62 +/- 0.38 SD score) was decreased compared with that in age-matched healthy subjects. The basal IGFBP-3 levels in the peripheral vein (4.50 +/- 0.33 mg/L) were within the normal range. There was a significant correlation 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 micrograms/min, whereas no basal net exchanges of IGF-I or IGFBP-3 were observed across the splanchnic area. Insulin inhibited splanchnic IGFBP-1 production within 120 min and glucose output within 20 min. Serum IGF-I, but not IGFBP-3, concentrations increased significantly during the insulin infusion. In summary, this study demonstrates the existence of considerable IGFBP-1 production from the liver during insulinopenia and the complete blocking of splanchnic IGFBP-1 production and increases in 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carrier Proteins / biosynthesis*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / metabolism*
  • Glucagon / blood
  • Glucose / biosynthesis
  • Hepatic Veins
  • Humans
  • Insulin / blood
  • Insulin / pharmacology*
  • Insulin / therapeutic use
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I / biosynthesis*
  • Kinetics
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Splanchnic Circulation


  • Carrier Proteins
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I
  • Glucagon
  • Glucose