Chen Sheng-Song, Donmoyer Christine M, Pearson David A, Poole Adrian, Zhang Yiqun, Lacy D Brooks, McGuinness Owen P
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E286-95. doi: 10.1152/ajpendo.00286.2003. Epub 2003 Oct 7.
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.
长期全胃肠外营养（TPN）显著增强肝脏葡萄糖净摄取（NHGU）。尽管伴有高胰岛素血症，但感染会损害这种适应性增加。在未适应状态下，NHGU取决于当时的葡萄糖水平。我们的目的是确定对TPN的适应是否会改变NHGU对葡萄糖的依赖性，感染是否会损害这种依赖性，以及在感染期间胰岛素是否调节NHGU对葡萄糖的依赖性。长期插管的犬接受TPN 5天。在TPN第3天，犬接受细菌纤维蛋白凝块以诱导非致死性感染（感染组，n = 9）或无菌纤维蛋白凝块（假手术组，n = 6）。植入凝块42小时后，输注生长抑素。在假手术组，输注胰岛素和胰高血糖素以使其水平与假手术组所见水平匹配（分别为9±1微单位/毫升和23±4皮克/毫升）。在感染动物中，要么输注胰岛素和胰高血糖素以使其水平与感染组所见水平匹配（25±2微单位/毫升和101±15皮克/毫升；感染高胰岛素组；n = 5），要么将胰岛素替代为与假手术组较低水平匹配（13±2微单位/毫升），而胰高血糖素保持升高（97±9皮克/毫升；感染低胰岛素组；n = 4）。然后进行四步（每步90分钟）高血糖（120、150、200或250毫克/分升）钳夹。在假手术组中，每个葡萄糖步骤时NHGU均增加（从3.6±0.6至5.4±0.7至8.9±0.9至12.1±1.1毫克·千克⁻¹·分钟⁻¹）；葡萄糖水平与NHGU之间关系的斜率（即葡萄糖依赖性）高于未适应动物。感染损害了感染高胰岛素组（1.3±0.4至2.9±0.5至5.5±1.0至7.7±1.6毫克·千克⁻¹·分钟⁻¹）和感染低胰岛素组（0.5±0.7至2.2±0.6至4.2±1.0至5.8±0.8毫克·千克⁻¹·分钟⁻¹）中葡萄糖依赖性NHGU。总之，TPN增强葡萄糖依赖性NHGU，感染的存在降低葡萄糖依赖性NHGU，并且与感染相关的伴随高胰岛素血症不能维持NHGU对葡萄糖的依赖性。
