Hepatic production and intestinal uptake of IGF-I: response to infection.

The role of the liver and gut in contributing to the infection-induced fall in circulating insulin-like growth factor I (IGF-I) was examined in chronically catheterized conscious dogs. Two weeks before study, catheters and Doppler flow probes were implanted to assess hepatic and gut balance of IGF-I. To control nutrient intake, dogs were placed on total parenteral nutrition (TPN) as their sole caloric source. After dogs received TPN for 5 days, net hepatic and intestine IGF-I balances were assessed. A hypermetabolic infected state was then induced by the intraperitoneal implantation of a fibrin clot containing Escherichia coli. TPN was continued, and organ IGF-I balance was assessed 24 and 48 h after induction of infection. Arterial IGF-I levels were significantly decreased following infection (111 ± 18, 62 ± 10, and 63 ± 8 ng/ml before and 24 and 48 h after, respectively). Net hepatic IGF-I output decreased markedly (221 ± 73, to 73 ± 41 and 41 ± 17 ng ⋅ kg-1 ⋅ min-1before and 24 and 48 h after, respectively). The infection-induced decrease in hepatic IGF-I output could not be explained by concomitant alterations in plasma cortisol or insulin levels. The gut demonstrated a net uptake of IGF-I before infection (178 ± 29 ng ⋅ kg-1 ⋅ min-1). However, after infection, intestinal IGF-I uptake was completely suppressed (-10 ± 15 and -8 ± 36 ng ⋅ kg-1 ⋅ min-1). In summary, infection decreases net hepatic IGF-I release 65-80% and completely suppresses net IGF-I uptake by the intestine. As a consequence of these reciprocal changes in IGF-I balance across the liver and intestine, splanchnic production of IGF-I was unchanged by infection. These data suggest that changes in the clearance and/or production of IGF-I by extrasplanchnic tissues contribute to the infection-induced decrease in circulating IGF-I levels.