Hamblin P S, Ozawa Y, Jefferds A, Mariash C N
Department of Medicine, University of Minnesota, Minneapolis 55455.
J Biol Chem. 1989 Dec 25;264(36):21646-51.
We have examined the mechanism of the carbohydrate induction of rat hepatic mRNA-S14 to the intragastric administration of sucrose and its constituent hexoses, fructose and glucose. A maximal sucrose response (26-fold) was obtained with 2 ml of 60% sucrose/100 g of body weight, yet equimolar concentrations of fructose and glucose were not able to reproduce the response. Fructose yielded less than one-third the response observed with sucrose, whereas glucose administration was ineffective. On the other hand, the simultaneous administration of both hexoses restored the full response observed with sucrose. The synergism between fructose and glucose was not due to the administration of extra calories or enhanced insulin release but was correlated with altered carbohydrate metabolism as reflected by the hepatic pyruvate content (0.058 +/- 0.003 mumol/g fasting, 0.067 +/- 0.009 glucose treated, 0.218 +/- 0.030 fructose treated, 0.292 +/- 0.015 sucrose treated). The time course of induction of mRNA-S14 nuclear precursor in response to fructose, glucose, or sucrose correlated with the mature mRNA-S14 values. In addition, enhanced transcriptional activity of the S14 gene was observed after sucrose feeding (from 25 +/- 8 ppm baseline to 108 +/- 40 ppm at 4 h) and fructose feeding (40 +/- 21 ppm at 4 h). These studies demonstrate that the carbohydrate regulation of mRNA-S14 is due to a synergistic interaction between fructose and glucose reflected in the hepatic pyruvate content and leading to the induction of the nuclear precursor with an associated increase in transcriptional activity of the S14 gene.
我们研究了大鼠肝脏mRNA-S14在经胃内给予蔗糖及其组成己糖（果糖和葡萄糖）后碳水化合物诱导的机制。给予2 ml 60%蔗糖/100 g体重时可获得最大的蔗糖反应（26倍），然而等摩尔浓度的果糖和葡萄糖无法重现该反应。果糖产生的反应不到蔗糖的三分之一，而给予葡萄糖则无效。另一方面，同时给予两种己糖可恢复观察到的蔗糖的完全反应。果糖和葡萄糖之间的协同作用并非由于额外热量的给予或胰岛素释放的增强，而是与碳水化合物代谢的改变相关，这可通过肝脏丙酮酸含量反映出来（空腹时为0.058±0.003 μmol/g，葡萄糖处理后为0.067±0.009，果糖处理后为0.218±0.030，蔗糖处理后为0.292±0.015）。响应果糖、葡萄糖或蔗糖诱导的mRNA-S14核前体的时间进程与成熟的mRNA-S14值相关。此外，在给予蔗糖（从基线的25±8 ppm在4小时时升至108±40 ppm）和果糖（在4小时时为40±21 ppm）后观察到S14基因的转录活性增强。这些研究表明，mRNA-S14的碳水化合物调节是由于果糖和葡萄糖之间的协同相互作用，这反映在肝脏丙酮酸含量中，并导致核前体的诱导以及S14基因转录活性的相关增加。
