Eastman R C, Carson R E, Orloff D G, Cochran C S, Perdue J F, Rechler M M, Lanau F, Roberts C T, Shapiro J, Roth J
Diabetes Branch, National Institute of Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Invest. 1992 Jun;89(6):1958-63. doi: 10.1172/JCI115803.
Tumor glucose use in patients with non-islet-cell tumors has been difficult to measure, particularly in hepatoma, because of hepatic involvement by neoplasm. We studied a patient with nonhepatic recurrence of hepatoma after successful liver transplantation. Tumor tissue contained messenger RNA for insulin-like growth factor-II (IGF-II), and circulating high molecular weight components and E-peptide of IGF-II were increased. Glucose use measured by isotope dilution with [3-3H]glucose was 7.94 mg/kg fat-free mass per min, and splanchnic glucose production was 0.93 mg/kg fat-free mass per min. Glucose uptake and glucose model parameters were independently measured in tissues by positron emission tomography with 18F-fluoro-2-deoxy-D-glucose. Glucose uptake by heart muscle, liver, skeletal muscle, and neoplasm accounted for 0.8, 14, 44, and 15% of total glucose use, respectively. Model parameters in liver and neoplasm were not significantly different, and glucose transport and phosphorylation were twofold and fourfold greater than in muscle. This suggests that circulating IGF-II-like proteins are partial insulin agonists, and that hypoglycemia in hepatoma with IGF-II production is predominantly due to glucose uptake by skeletal muscle and suppression of glucose production.
由于肿瘤累及肝脏,非胰岛细胞瘤患者的肿瘤葡萄糖利用情况一直难以测量,尤其是在肝癌患者中。我们研究了一名肝移植成功后出现非肝性肝癌复发的患者。肿瘤组织含有胰岛素样生长因子-II(IGF-II)的信使核糖核酸,循环中的高分子量成分和IGF-II的E肽增加。用[3-3H]葡萄糖通过同位素稀释法测得的葡萄糖利用率为每分钟7.94毫克/千克去脂体重,内脏葡萄糖生成率为每分钟0.93毫克/千克去脂体重。通过18F-氟-2-脱氧-D-葡萄糖正电子发射断层扫描独立测量组织中的葡萄糖摄取和葡萄糖模型参数。心肌、肝脏、骨骼肌和肿瘤的葡萄糖摄取分别占总葡萄糖利用的0.8%、14%、44%和15%。肝脏和肿瘤中的模型参数无显著差异,葡萄糖转运和磷酸化分别比肌肉中的高两倍和四倍。这表明循环中的IGF-II样蛋白是部分胰岛素激动剂,并且产生IGF-II的肝癌患者发生低血糖主要是由于骨骼肌摄取葡萄糖和抑制葡萄糖生成。