REGULATION OF THE INSULIN-LIKE GROWTH-FACTOR SYSTEM BY INSULIN IN BURN PATIENTS

The aim of the present investigation was to determine whether there is a net uptake of insulin-like growth factor I (IGF-I) or IGF-binding p roteins (IGFBPs) by the leg after burn injury and to elucidate the reg ulatory role of insulin exerted on this system under in vivo condition s in burn patients. Studies were performed on nine patients after burn injury (similar to 60% body surface area). Each patient was studied t wice during a continuous infusion of a carbohydrate-rich enteral diet. Blood was collected simultaneously from the femoral artery and vein f or the measurement of various elements of the IGF system after 7 days of enteral diet alone (basal period) and after 7 days of the enteral d iet plus the infusion of insulin (insulin period). Data from these pat ients were compared to values in age-matched fed healthy volunteers. D uring the basal period, burn patients demonstrated a significant reduc tion in the venous concentration of IGF-I and an increase in both IGFB P-1 and -2 compared to control values. Insulin produced a significant 15% increase in the IGF-I concentration in burn patients, but decrease d the circulating levels of IGFBP-1 by 50%. The IGF-I and IGFBP-1 conc entrations at the end of the insulin period were still significantly d ifferent from those in control subjects. Burn patients also exhibited a marked reduction in intact IGFBP-3 and the acid-labile subunit under basal conditions, and these alterations were not reversed by insulin. Under basal conditions, all burn patients had a positive arterio-veno us (A-V) difference for IGF-I across the leg. The A-V difference was i ncreased 50% in response to insulin. The net uptake of IGF-I by the le g was 2.4 mu g/min under basal conditions, and as leg blood flow also tended to increase in response to insulin, IGF-I uptake was elevated m ore than 3-fold during the insulin period. No A-V difference across th e leg was detected for IGFBP-1, -2, or -3 in burn patients. In conclus ion, burn injury in humans produces dramatic and sustained alterations in various components of the IGF system that persist despite adequate nutritional support. Our data indicate the presence of a net uptake o f IGF-I by the leg in burn patients that may serve to counteract the c atabolic state.