title: Hepatic production and intestinal uptake of IGF-I: response to infection.
abstract: 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-1 before 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.
authors.affiliation: Departments of Cellular and Molecular Physiology and Surgery, Pennsylvania State College of Medicine, Hershey, Pennsylvania 17033-0850, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Lang
authors.forename: R A
authors.initials: RA
authors.lastname: Frost
authors.forename: J
authors.initials: J
authors.lastname: Ejiofor
authors.forename: D B
authors.initials: DB
authors.lastname: Lacy
authors.forename: O P
authors.initials: OP
authors.lastname: McGuinness
mesh_terms: D000818:Animals; D004285:Dogs; D004927:Escherichia coli Infections / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D005934:Glucagon / Q000097:blood; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation / Q000502:physiology; D012016:Reference Values; D012039:Regional Blood Flow / Q000502:physiology
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D005934:Glucagon; D006854:Hydrocortisone