Minderop R H, Hoeppner W, Seitz H J
Eur J Biochem. 1987 Apr 1;164(1):181-7. doi: 10.1111/j.1432-1033.1987.tb11009.x.
The present study investigates the effect of thyroid and glucocorticoid hormones on the induction of hepatic glucokinase mRNA activity, enzyme synthesis and activity in starved/refed adrenalectomized, thyroidectomized and intact rats. In intact rats glucose refeeding resulted within 2 h in a more than tenfold increase in the functional messenger, followed by a corresponding increase in glucokinase synthesis and, a little later, in enzyme activity. Glucokinase mRNA and synthesis remained elevated at this level for about further 6 h. Then the mRNA activity and enzyme synthesis declined considerably to a new steady state (a factor of about 4 above the starvation level) within a further 8 h, while enzyme activity remained constantly elevated. The half-life of glucokinase mRNA, as determined after administration of cordycepin, was identical during the different refeeding periods. Thus the overshoot phenomenon, provoked by carbohydrate refeeding, in glucokinase mRNA is not explained by alteration of the glucokinase mRNA decay rates. In thyroidectomized or adrenalectomized rats, glucose refeeding resulted in only a small increase in glucokinase mRNA, synthesis and activity. Application of thyroid hormones in thyroidectomized rats, refed a carbohydrate-rich diet, enhanced the specific mRNA considerably within 8-10 h, while it took 20-24 h to enhance glucokinase mRNA by glucocorticoids in adrenalectomized rats refed a carbohydrate-rich diet. The decay in translatable glucokinase mRNA, as determined after administration of cordycepin, was identical in the hypothyroid and euthyroid fed state, while adrenalectomy resulted in a significant decrease in the specific mRNA half-life. We conclude that refeeding a carbohydrate-rich diet rapidly stimulates glucokinase mRNA regeneration showing overshoot kinetics. 3,3',5-Triiodothyronine in its physiological concentration significantly enhances the response in glucokinase mRNA at the nuclear level, while glucocorticoids in their physiological concentration predominantly stabilize the translatable glucokinase mRNA.
本研究调查了甲状腺激素和糖皮质激素对饥饿/再喂食的肾上腺切除、甲状腺切除及完整大鼠肝脏葡萄糖激酶mRNA活性、酶合成及活性诱导的影响。在完整大鼠中，重新喂食葡萄糖2小时内，功能性信使增加了十多倍，随后葡萄糖激酶合成相应增加，稍晚些时候酶活性也增加。葡萄糖激酶mRNA和合成在该水平保持升高约6小时。然后mRNA活性和酶合成在接下来的8小时内大幅下降至新的稳态（比饥饿水平高约4倍），而酶活性持续升高。给予放线菌素D后测定的葡萄糖激酶mRNA半衰期在不同的再喂食阶段相同。因此，碳水化合物再喂食引发的葡萄糖激酶mRNA过冲现象并非由葡萄糖激酶mRNA降解速率的改变所致。在甲状腺切除或肾上腺切除的大鼠中，重新喂食葡萄糖仅导致葡萄糖激酶mRNA、合成及活性小幅增加。在喂食富含碳水化合物饮食的甲状腺切除大鼠中应用甲状腺激素，8 - 10小时内可显著增强特异性mRNA，而在喂食富含碳水化合物饮食的肾上腺切除大鼠中，糖皮质激素需要20 - 24小时才能增强葡萄糖激酶mRNA。给予放线菌素D后测定的可翻译葡萄糖激酶mRNA的衰减在甲状腺功能减退和甲状腺功能正常的喂食状态下相同，而肾上腺切除导致特异性mRNA半衰期显著缩短。我们得出结论，喂食富含碳水化合物的饮食可迅速刺激葡萄糖激酶mRNA再生，呈现过冲动力学。生理浓度的3,3',5 - 三碘甲状腺原氨酸在核水平显著增强葡萄糖激酶mRNA的反应，而生理浓度的糖皮质激素主要稳定可翻译的葡萄糖激酶mRNA。
