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Time course of the hepatic adaptation to TPN: interaction with glycogen depletion

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee

Submitted 3 May 2004 ; accepted in final form 17 August 2004

In response to chronic (5 days) TPN, the liver becomes a major site of glucose disposal, removing 45% (4.5 mg·kg^–1·min^–1) of exogenous glucose. Moreover, 70% of glucose is not stored but released as lactate. We aimed to determine in chronically catheterized conscious dogs the time course of adaptation to TPN and the glycogen depletion impact on early time course. After an 18-h (n = 5) fast, TPN was infused into the inferior vena cava for 8 (n = 5) or 24 h (n = 6). A third group, of 42-h-fasted animals (n = 6), was infused with TPN for 8 h. TPN was infused at a rate designed to match the dog's calculated basal energy and nitrogen requirements. NHGU (–2.3 ± 0.1 to 2.2 ± 0.7 to 3.9 ± 0.6 vs. –1.7 ± 0.3 to 1.1 ± 0.5 to 2.9 ± 0.4 mg·kg^–1·min^–1, basal to 4 to 8 h, 18 vs. 42 h) and net hepatic lactate release (0.7 ± 0.3 to 0.6 ± 0.1 to 1.4 ± 0.2 vs. –0.6 ± 0.1 to 0.1 ± 0.1 to 0.8 ± 0.1 mg·kg^–1·min^–1, basal to 4 to 8 h) increased progressively. Net hepatic glycogen repletion and tracer determined that glycogen syntheses were similar. After 24 h of TPN, NHGU (5.4 ± 0.6 mg·kg^–1·min^–1) and net hepatic lactate release (2.6 ± 0.4 mg·kg^–1·min^–1) increased further. In summary, 1) most hepatic adaptation to TPN occurs within 24 h after initiation of TPN, and 2) prior glycogen depletion does not augment hepatic adaptation rate.

nutritional support; glucagon

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