Splanchnic exchange of insulin-like growth factor binding protein-1 (IGFBP-1), IGF-I and acid-labile subunit (ALS) during normo- and hyper-insulinaemia in healthy subjects

OBJECTIVE: The main source of circulating IGF-I, insulin like growth factor binding protein-1 (IGFBP-1) and acid-labile subunit (ALS) is considered to be the liver, but their production rates have not been determined in healthy individuals. Thus, the splanchnic exchange of IGFBP-1, IGF-I, ALS and glucose were studied. STUDY DESIGN: In five overnight fasting healthy, normal weight men (mean age 29 +/- 1 years) blood samples were taken from a hepatic vein, a brachial artery and a peripheral vein in the basal state and during 3 h i.v. infusion of insulin (1.0 mU/kg/min). Normoglycaemia was maintained with a variable glucose infusion and splanchnic blood flow was determined using a constant rate indicator infusion technique. RESULTS: The basal net splanchnic glucose output amounted 0.96 +/- 0. 09 mmol/min and the splanchnic production of IGFBP-1 was 7 +/- 2 microg/min. There was a net splanchnic uptake of IGF-I (7 +/- 2 microg/min) in the basal state, while no significant splanchnic exchange of ALS was found. During the insulin infusion, insulin concentration increased from 78 +/- 12 to 660 +/- 30 pmol/l, resulting in a complete inhibition of splanchnic glucose production after 40 min of infusion. Splanchnic IGFBP-1 production rose initially to 13 +/- 4 microg/min (P < 0.05) and then gradually decreased and was completely inhibited at 180 min (P < 0.05). Insulin infusion influenced neither ALS nor IGF-I splanchnic exchange. CONCLUSION: Splanchnic production of IGFBP-1 in the basal state was demonstrated and it is completely inhibited after 180 min of hyperinsulinaemia. In contrast to what is generally held, there was no net splanchnic production of IGF-I in the basal state or during insulin stimulation.