大鼠 Walker-256 肿瘤发展过程中肝脏糖异生的变化。
Changes in liver gluconeogenesis during the development of Walker-256 tumour in rats.
机构信息
Department of Physiological Sciences, State University of Londrina, Londrina, Brazil.
出版信息
Int J Exp Pathol. 2013 Feb;94(1):47-55. doi: 10.1111/iep.12002.
Few studies have investigated liver gluconeogenesis in cancer and there is no agreement as to whether the activity of this pathway is increased or decreased in this disease. The aim of this study was to evaluate gluconeogenesis from alanine, pyruvate and glycerol, and related metabolic parameters in perfused liver from Walker-256 tumour-bearing rats on days 5 (WK5 group), 8 (WK8 group) and 12 (WK12 group) of tumour development. There was reduction (P < 0.05) of liver glucose production from alanine and pyruvate in WK5, WK8 and WK12 groups, which was accompanied by a decrease (P < 0.05) in oxygen consumption. Moreover, there was higher (P < 0.05) pyruvate and lactate production from alanine in the WK5 group and a marked reduction (P < 0.05) of pyruvate and urea production from alanine in the WK12 group. In addition, liver glucose production and oxygen consumption from glycerol were not reduced in WK5, WK8 and WK12 groups. Thus the, the results show inhibition of hepatic gluconeogenesis from alanine and pyruvate, but not from glycerol, on days 5, 8 and 12 of Walker-256 tumour development, which can be attributed to the metabolic step in which the substrate enters the gluconeogenic pathway.
很少有研究调查癌症中的肝脏糖异生，对于该疾病中该途径的活性是增加还是减少尚无定论。本研究旨在评估 Walker-256 肿瘤荷瘤大鼠在肿瘤发展第 5 天（WK5 组）、第 8 天（WK8 组）和第 12 天（WK12 组）的灌流肝脏中丙氨酸、丙酮酸和甘油的糖异生以及相关代谢参数。在 WK5、WK8 和 WK12 组中，肝脏对丙氨酸和丙酮酸的葡萄糖生成减少（P<0.05），这伴随着氧消耗的减少（P<0.05）。此外，在 WK5 组中，丙氨酸转化为丙酮酸和乳酸的产量增加（P<0.05），而在 WK12 组中，丙氨酸转化为丙酮酸和尿素的产量显著减少（P<0.05）。此外，在 WK5、WK8 和 WK12 组中，肝脏从甘油产生的葡萄糖和氧气消耗并未减少。因此，结果表明在 Walker-256 肿瘤发展的第 5、8 和 12 天，肝脏从丙氨酸和丙酮酸的糖异生受到抑制，但从甘油的糖异生不受抑制，这可能归因于底物进入糖异生途径的代谢步骤。
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