Kinlaw W B, Perez-Castillo A M, Fish L H, Mariash C N, Schwartz H L, Oppenheimer J H
Department of Medicine, University of Minnesota, Minneapolis 55455.
Mol Endocrinol. 1987 Sep;1(9):609-13. doi: 10.1210/mend-1-9-609.
The mRNA of the rat hepatic S14 gene accumulates rapidly after administration of T3 and carbohydrate, making it an excellent model for studies of the effects of dietary and hormonal stimuli at the hepatocellular level. We undertook studies to assess circadian changes in responsivity of this sequence to intragastric sucrose administration combined with insulin injection, and evaluated the capacity of glucagon to reverse these effects. As in the case of T3, the response of mRNA-S14 to carbohydrate in the morning was brisk whereas there was no significant increment when the stimulus was applied in the evening. In confirmation of previous studies, glucagon markedly lowered levels of mRNA-S14 in the evening but exerted no effect in the morning. These results support the concept that the rate of hepatic production of mRNA-S14 in unmanipulated rats is maximal in the evening, thus allowing no further induction by carbohydrate or T3 but permitting reduction by glucagon. Conversely, the rate of production is minimal in the morning, permitting induction by carbohydrate or T3 but allowing no further reduction by glucagon. A major difference between the effects of carbohydrate and those of T3 was the observed failure of carbohydrate to reverse the effect of glucagon in the evening. The effect of glucagon was stimulated by (Bu)2cAMP, and this was reversed by T3. However, T3 did not modify the glucagon-induced increase in hepatic cAMP levels. We therefore conclude that the capacity of T3 to abolish the glucagon effect is mediated at a step distal to the generation of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
给予三碘甲状腺原氨酸（T3）和碳水化合物后，大鼠肝脏S14基因的信使核糖核酸（mRNA）迅速积累，这使其成为在肝细胞水平研究饮食和激素刺激作用的优秀模型。我们进行了研究，以评估该序列对胃内给予蔗糖并联合注射胰岛素的反应性的昼夜变化，并评估胰高血糖素逆转这些作用的能力。与T3的情况一样，mRNA-S14在早晨对碳水化合物的反应迅速，而在晚上给予刺激时则没有显著增加。正如先前研究所证实的，胰高血糖素在晚上显著降低了mRNA-S14的水平，但在早晨没有作用。这些结果支持了这样一种观点，即在未受处理的大鼠中，mRNA-S14的肝脏产生速率在晚上最大，因此不再受碳水化合物或T3的进一步诱导，但可被胰高血糖素降低。相反，产生速率在早晨最小，允许碳水化合物或T3诱导，但不再被胰高血糖素进一步降低。碳水化合物和T3作用之间的一个主要差异是，观察到碳水化合物在晚上不能逆转胰高血糖素的作用。（二丁酰）环磷腺苷（（Bu）2cAMP）刺激了胰高血糖素的作用，而T3可逆转这种作用。然而，T3并未改变胰高血糖素诱导的肝脏环磷腺苷（cAMP）水平升高。因此，我们得出结论，T3消除胰高血糖素作用的能力是在cAMP产生的远端步骤介导的。（摘要截短于250字）
