title: Infection impairs insulin-dependent hepatic glucose uptake during total parenteral nutrition.
abstract: Total parenteral nutrition (TPN) markedly augments net hepatic glucose uptake (NHGU) and hepatic glycolysis in the presence of mild hyperglycemia and hyperinsulinemia. This increase is impaired by an infection. We determined whether the adaptation to TPN alters the responsiveness of the liver to insulin and whether infection impairs that response. Chronically catheterized dogs received TPN for 5 days. On day 3 of TPN, either a nonlethal hypermetabolic infection was induced (INF, n = 5) or a sham surgery was performed (SHAM, n = 5). Forty-two hours after clot implantation, somatostatin and glucagon (34 +/- 3 vs. 84 +/- 11 pg/ml in artery, SHAM vs. INF) were infused, and a three-step (120 min each) isoglycemic (approximately 120 mg/dl) hyperinsulinemic (approximately 12, 25, and 50 microU/ml) clamp was performed to simulate levels seen in normal, infected, and exogenous insulin treatment states. In SHAM, NHGU (3.5 +/- 0.2 to 4.2 +/- 0.4 to 4.6 +/- 0.5 mg x kg(-1) x min(-1)) modestly increased. In INF, NHGU was consistently lower at each insulin step (1.1 +/- 0.5 to 2.6 +/- 0.5 to 2.8 +/- 0.7 mg x kg(-1) x min(-1)). Although NHGU increased from the first to the second step in INF, it did not increase further with the highest dose of insulin. Despite increases in NHGU, net hepatic lactate release did not increase in SHAM and fell in INF. In summary, in the TPN-adapted state, liver glucose uptake is unresponsive to increases in insulin above the basal level. Although the infection-induced increase in insulin sustains NHGU, further increments in insulin enhance neither NHGU nor glycolysis.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Donmoyer
authors.forename: Sheng-Song
authors.initials: SS
authors.lastname: Chen
authors.forename: D Brooks
authors.initials: DB
authors.lastname: Lacy
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: Owen P
authors.initials: OP
authors.lastname: McGuinness
mesh_terms: D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004927:Escherichia coli Infections / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006614:Hindlimb / Q000378:metabolism; D006728:Hormones / Q000097:blood; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D010289:Parenteral Nutrition, Total
chemical_list: D006728:Hormones; D007328:Insulin; D005947:Glucose