DIRECT INFUSION OF A VARIANT OF INSULIN-LIKE GROWTH FACTOR-I INTO THESKIN OF SHEEP AND EFFECTS ON LOCAL BLOOD-FLOW, AMINO-ACID UTILIZATIONAND CELL REPLICATION

In vivo effects of local infusion of a variant of insulin-like growth factor-I (IGF-I), long-R3-IGF-I, into the skin were investigated using six conscious sheep with food available ad libitum. An artery and vei n on the abdominal flank of each animal, as well as the saphenous arte ry, were catheterized so that infusion of isotopically labelled amino acids, with or without IGF-I, could be used to determine amino acid up take by arteriovenous difference in combination with blood flow determ ined by dye dilution. Measurements were made on each animal prior to I GF-I infusion, at hourly intervals for the 4 h of IGF-I infusion into the skin artery, then 2 and 4 h after IGF-I infusion ceased. Numbers o f cells replicating in the bulbs of wool follicles in the IGF-I-infuse d area and in the skin on the contralateral side of each animal were m easured after labelling with 5-bromo-2'-deoxyuridine. IGF-I caused a s ignificant increase in the skin blood flow (P<0.05), utilization of ox ygen (P<0.05), uptake of cysteine (P<0.05) and phenylalanine (P<0.001) , and the rate of utilization of cysteine (P<0.05) for protein synthes is. IGF-I increased amino acid uptake regardless of whether the skin w as in negative or positive amino acid balance prior to infusion. Durin g the recovery period amino acid utilization by skin returned towards preinfusion levels. No effects of IGF-I were found on replicating cell numbers in the bulbs of wool follicles.