Torosian M H, Bartlett D L, Chatzidakis C, Stein T P
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia.
J Surg Res. 1993 Jul;55(1):68-73. doi: 10.1006/jsre.1993.1110.
Futile cycling of metabolic substrates may play an important role in the development of cancer cachexia. To determine the effect of tumor burden on futile glucose and lipid cycling, 64 female Lewis/Wistar rats were randomized to control (non-tumor-bearing), small tumor burden, or large tumor burden groups (MAC-33 mammary adenocarcinoma). After 5 or 25 days of tumor growth, animals received a 5-day period of parenteral nutrition (158 kcal/kg/day) followed by a 6-hr infusion of the stable isotopes glucose-2-d and glucose-6,6-d2 or [C13]palmitate. The heavy glucose isotopes glucose-2-d and glucose-6,6-d2 are labeled with deuterium at the 2-carbon position and doubly labeled with deuterium at the 6-carbon position, respectively, to obtain differential molecular weights. No increase in glucose or lipid cycling was observed in animals with small tumor burdens. In contrast, a significant increase in plasma rate of appearance (Ra) of glucose-2-d (1377 +/- 136 mg/hr vs 947 +/- 54 mg/hr), Ra of glucose-6,6-d2 (810 +/- 88 mg/hr vs 510 +/- 24 mg/hr), and total glucose cycling (548 +/- 57 mg/hr vs 416 +/- 28 mg/hr) was seen in animals with large tumor burdens compared to control animals (P < 0.05). Although a trend toward increased lipid cycling was seen in tumor-bearing versus control animals, this change was not significant. Thus, futile cycling of glucose was significantly elevated in animals with large tumor burdens and may cause significant energy wasting to contribute to the development of cachexia in the tumor-bearing host.
代谢底物的无效循环可能在癌症恶病质的发展中起重要作用。为了确定肿瘤负荷对葡萄糖和脂质无效循环的影响，将64只雌性Lewis/Wistar大鼠随机分为对照组（无肿瘤）、小肿瘤负荷组或大肿瘤负荷组（MAC - 33乳腺腺癌）。肿瘤生长5天或25天后，动物接受为期5天的肠外营养（158千卡/千克/天），随后静脉输注稳定同位素葡萄糖 - 2 - d和葡萄糖 - 6,6 - d2或[C13]棕榈酸6小时。重葡萄糖同位素葡萄糖 - 2 - d和葡萄糖 - 6,6 - d2分别在2 - 碳位置用氘标记，在6 - 碳位置用氘双重标记，以获得不同的分子量。小肿瘤负荷的动物未观察到葡萄糖或脂质循环增加。相比之下，与对照动物相比，大肿瘤负荷的动物中葡萄糖 - 2 - d的血浆出现率（Ra）显著增加（1377±136毫克/小时对947±54毫克/小时），葡萄糖 - 6,6 - d2的Ra（810±88毫克/小时对510±24毫克/小时），以及总葡萄糖循环（548±57毫克/小时对416±28毫克/小时）（P < 0.05）。虽然在荷瘤动物与对照动物中观察到脂质循环有增加的趋势，但这种变化不显著。因此，大肿瘤负荷动物的葡萄糖无效循环显著升高，可能导致大量能量浪费，从而促进荷瘤宿主恶病质的发展。
