Hepatic and muscle glucose metabolism during total parenteral nutrition: impact of infection

We examined the impact of infection on hepatic and muscle glucose metabolism in dogs adapted to chronic total parenteral nutrition (TPN). Studies were done in five conscious chronically catheterized dogs, in which sampling (artery, portal and hepatic vein, and iliac vein), infusion catheters (inferior vena cava), and Transonic flow probes (hepatic artery, portal vein, and iliac artery) were implanted. Fourteen days after surgery, dogs were placed on TPN. After 5 days of TPN, an infection was induced, and the TPN was continued. The balance of substrates across the liver and limb was assessed on the day before infection (day 0) and 18 (day I) and 42 h (day 2) after infection. On day 0, the liver was a marked net consumer of glucose (4.3 +/- 0.6 mg.kg(-1).min(-1)) despite near normoglycemia (117 +/- 5 mg/dl) and only mild hyperinsulinemia (16 +/- 2 mu U/ml). In addition, the majority (79 +/- 13%) of the glucose taken up by the liver was released as lactate (34 +/- 6 mu mol.kg(-1).min(-1)). After infection, net hepatic glucose uptake decreased markedly on day 1 (1.6 +/-. 0.9 mg.kg(-1).min(-1)) and remained suppressed on clay 2 (2.4 +/- 0.5 mg.kg(-1).min(-1)). Net hepatic lactate output also decreased on days 1 and 2 (15 +/- 5 and 12 +/- 3 mu mol.kg(-1).min(-1), respectively). This occurred despite increases in arterial plasma glucose on days 1 and 2 (135 +/- 9 and 144 +/- 9 mg/dl, respectively) and insulin levels on days 1 and 2 (57 +/- 14 and 34 +/- 9 mu U/ml, respectively). In summary, the liver undergoes a profound adaptation to TPN, making it a major site of glucose disposal and conversion to lactate. Infection impairs hepatic glucose uptake, forcing TPN-derived glucose to be removed by peripheral tissues.