Munnich A, Lyonnet S, Chauvet D, Van Schaftingen E, Kahn A
Institut National de la Santé et de la Recherche Médicale U-129 24.
J Biol Chem. 1987 Dec 15;262(35):17065-71.
Dietary carbohydrates are known to stimulate L-type pyruvate kinase gene expression at the transcriptional level in the liver. However, the short-term effects, the time course, and the mechanism of the gene activation by elemental hexoses in normal fasted rats remain unknown. In the present study, both glucose and fructose were found to stimulate the gene expression at the transcriptional level in liver. However, the kinetics and the extent of the mRNA induction differed according to the carbohydrate given. Fructose stimulated early (2-4 h) and transiently the gene transcription, the RNA precursor, and the mRNA accumulation in 48-h-fasted rats while maximum stimulation of the RNA synthesis by glucose was delayed until the 12th h of refeeding, despite an early rise of plasma insulin. In contrast, insulin release was not required for fructose to trigger the gene transcription, nor did the high cyclic AMP levels in fasted rat liver prevent RNA synthesis by fructose. The agent(s) operating early in fructose-fed animals might be powerful enough to not require insulin for gene activation and to balance the inhibitory action of glucagon in the liver.
已知膳食碳水化合物可在转录水平上刺激肝脏中L型丙酮酸激酶基因的表达。然而,在正常禁食大鼠中,单糖对该基因激活的短期效应、时间进程和机制仍不清楚。在本研究中,发现葡萄糖和果糖均可在转录水平上刺激肝脏中的基因表达。然而,mRNA诱导的动力学和程度因给予的碳水化合物不同而有所差异。果糖在禁食48小时的大鼠中可早期(2 - 4小时)且短暂地刺激基因转录、RNA前体及mRNA积累,而尽管血浆胰岛素早期升高,但葡萄糖对RNA合成的最大刺激作用延迟至再喂养的第12小时。相反,果糖触发基因转录并不需要胰岛素释放,禁食大鼠肝脏中高浓度的环磷酸腺苷水平也不会阻止果糖进行RNA合成。在喂食果糖的动物中早期起作用的因子可能足够强大,以至于不需要胰岛素来激活基因,并能平衡肝脏中胰高血糖素的抑制作用。