title: Impact of infection on glucose-dependent liver glucose uptake during TPN: interaction with insulin.
abstract: Chronic total parenteral nutrition (TPN) markedly augments net hepatic glucose uptake (NHGU). This adaptive increase is impaired by an infection despite accompanying hyperinsulinemia. In the nonadapted state, NHGU is dependent on the prevailing glucose levels. Our aims were to determine whether the adaptation to TPN alters the glucose dependence of NHGU, whether infection impairs this dependence, and whether insulin modulates the glucose dependence of NHGU during infection. Chronically catheterized dogs received TPN for 5 days. On day 3 of TPN, dogs received either a bacterial fibrin clot to induce a nonlethal infection (INF, n = 9) or a sterile fibrin clot (Sham, n = 6). Forty-two hours after clot implantation, somatostatin was infused. In Sham, insulin and glucagon were infused to match the level seen in Sham (9 +/- 1 microU/ml and 23 +/- 4 pg/ml, respectively). In infected animals, either insulin and glucagon were infused to match the levels seen in infection (25 +/- 2 microU/ml and 101 +/- 15 pg/ml; INF-HI; n = 5) or insulin was replaced to match the lower levels seen in Sham (13 +/- 2 microU/ml), whereas glucagon was kept elevated (97 +/- 9 pg/ml; INF-LO; n = 4). Then a four-step (90 min each) hyperglycemic (120, 150, 200, or 250 mg/dl) clamp was performed. NHGU increased at each glucose step in Sham (from 3.6 +/- 0.6 to 5.4 +/- 0.7 to 8.9 +/- 0.9 to 12.1 +/- 1.1 mg.kg(-1).min(-1)); the slope of the relationship between glucose levels and NHGU (i.e., glucose dependence) was higher than that seen in nonadapted animals. Infection impaired glucose-dependent NHGU in both INF-HI (1.3 +/- 0.4 to 2.9 +/- 0.5 to 5.5 +/- 1.0 to 7.7 +/- 1.6 mg.kg(-1).min(-1)) and INF-LO (0.5 +/- 0.7 to 2.2 +/- 0.6 to 4.2 +/- 1.0 to 5.8 +/- 0.8 mg.kg(-1).min(-1)). In summary, TPN augments glucose-dependent NHGU, the presence of infection decreases glucose-dependent NHGU, and the accompanying hyperinsulinemia associated with infection does not sustain the glucose dependence of NHGU.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: Sheng-Song
authors.initials: SS
authors.lastname: Chen
authors.forename: Christine M
authors.initials: CM
authors.lastname: Donmoyer
authors.forename: David A
authors.initials: DA
authors.lastname: Pearson
authors.forename: Adrian
authors.initials: A
authors.lastname: Poole
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Zhang
authors.forename: D Brooks
authors.initials: DB
authors.lastname: Lacy
authors.forename: Owen P
authors.initials: OP
authors.lastname: McGuinness
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004285:Dogs; D004347:Drug Interactions; D004927:Escherichia coli Infections / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D006439:Hemodynamics; D006614:Hindlimb / Q000098:blood supply; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007422:Intestines / Q000098:blood supply; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D010289:Parenteral Nutrition, Total
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D005947:Glucose