Petersen K F, Krssak M, Navarro V, Chandramouli V, Hundal R, Schumann W C, Landau B R, Shulman G I
Department of Internal Medicine, Yale University School of Medicine, New Haven, Conneticut 06520-8020, USA.
Am J Physiol. 1999 Mar;276(3):E529-35. doi: 10.1152/ajpendo.1999.276.3.E529.
Net hepatic glycogenolysis and gluconeogenesis were examined in normal (n = 4) and cirrhotic (n = 8) subjects using two independent methods [13C nuclear magnetic resonance spectroscopy (NMR) and a 2H2O method]. Rates of net hepatic glycogenolysis were calculated by the change in hepatic glycogen content before ( approximately 11:00 PM) and after ( approximately 7:00 AM) an overnight fast using 13C NMR and magnetic resonance imaging. Gluconeogenesis was calculated as the difference between the rates of glucose production determined with an infusion of [6,6-2H2]glucose and net hepatic glycogenolysis. In addition, the contribution of gluconeogenesis to glucose production was determined by the 2H enrichment in C-5/C-2 of blood glucose after intake of 2H2O (5 ml/kg body water). Plasma levels of total and free insulin-like growth factor I (IGF-I) and IGF-I binding proteins-1 and -3 were significantly decreased in the cirrhotic subjects (P < 0.01 vs. controls). Postprandial hepatic glycogen concentrations were 34% lower in the cirrhotic subjects (P = 0.007). Rates of glucose production were similar between the cirrhotic and healthy subjects [9.0 +/- 0.9 and 10.0 +/- 0.8 micromol. kg body wt-1. min-1, respectively]. Net hepatic glycogenolysis was 3.5-fold lower in the cirrhotic subjects (P = 0.01) and accounted for only 13 +/- 6% of glucose production compared with 40 +/- 10% (P = 0.03) in the control subjects. Gluconeogenesis was markedly increased in the cirrhotic subjects and accounted for 87 +/- 6% of glucose production vs. controls: 60 +/- 10% (P = 0.03). Gluconeogenesis in the cirrhotic subjects, as determined from the 2H enrichment in glucose C-5/C-2, was also increased and accounted for 68 +/- 3% of glucose production compared with 54 +/- 2% (P = 0.02) in the control subjects. In conclusion, cirrhotic subjects have increased rates of gluconeogenesis and decreased rates of net hepatic glycogenolysis compared with control subjects. These alterations are likely important contributing factors to their altered carbohydrate metabolism.
使用两种独立的方法[13C核磁共振波谱法（NMR）和2H2O法]，对正常受试者（n = 4）和肝硬化受试者（n = 8）的肝脏净糖原分解和糖异生进行了检测。通过13C NMR和磁共振成像，利用过夜禁食前（约晚上11:00）和禁食后（约早上7:00）肝脏糖原含量的变化，计算肝脏净糖原分解率。糖异生计算为输注[6,6-2H2]葡萄糖测定的葡萄糖生成率与肝脏净糖原分解率之间的差值。此外，通过摄入2H2O（5 ml/kg体重水）后血糖C-5/C-2中的2H富集情况，确定糖异生对葡萄糖生成的贡献。肝硬化受试者的血浆总胰岛素样生长因子I（IGF-I）、游离IGF-I以及IGF-I结合蛋白-1和-3水平显著降低（与对照组相比，P < 0.01）。肝硬化受试者餐后肝脏糖原浓度低34%（P = 0.007）。肝硬化受试者与健康受试者的葡萄糖生成率相似[分别为9.0±0.9和10.0±0.8 μmol·kg体重-1·min-1]。肝硬化受试者的肝脏净糖原分解率低3.5倍（P = 0.01），仅占葡萄糖生成的13±6%，而对照组为40±1%（P = 0.03）。肝硬化受试者的糖异生显著增加，占葡萄糖生成的87±6%，而对照组为60±10%（P = 0.03）。根据葡萄糖C-5/C-2中的2H富集情况确定，肝硬化受试者的糖异生也增加，占葡萄糖生成的68±3%，而对照组为54±2%（P = 0.02）。总之，与对照组相比，肝硬化受试者的糖异生率增加，肝脏净糖原分解率降低。这些改变可能是其碳水化合物代谢改变的重要促成因素。
