Newgard C B, Foster D W, McGarry J D
Diabetes. 1984 Feb;33(2):192-5. doi: 10.2337/diab.33.2.192.
The mechanism by which exogenous glucose stimulates the incorporation of hepatic glucose-6-phosphate into glycogen in fasted rats has not been clearly delineated. We gave glucose intragastrically over a 3.5-h period during which liver glycogen was deposited at linear rates. Simultaneous primed continuous infusion of [2-3H] or [3-3H]glucose established that under these conditions absolute carbon flow through hepatic glucose-6-phosphatase was greatly suppressed. After 1 h, hepatic [UDP-glucose] and [glucose-6-phosphate] had fallen by 50-60% and the former remained low throughout the experiment. By contrast, [glucose-6-phosphate] rebounded to its initial value by 2 h and remained at this level during the subsequent hour. We interpret the data as follows. Exogenous glucose, in addition to acting as a precursor of liver glucose-6-phosphate, causes diversion of the latter away from free glucose formation and into glycogen synthesis. The fall in [UDP-glucose] is in accord with a glucose-induced activation of glycogen synthase, as proposed by Hers (Annu. Rev. Biochem. 1976; 45:167-89.). However, the fall-rise sequence of glucose-6-phosphate concentration constitutes the first direct evidence in vivo for simultaneous inhibition at the level of glucose-6-phosphatase.
禁食大鼠中，外源性葡萄糖刺激肝葡萄糖-6-磷酸掺入糖原的机制尚未明确。我们在3.5小时内给大鼠灌胃葡萄糖，在此期间肝糖原以线性速率沉积。同时，用[2-³H]或[3-³H]葡萄糖进行预充连续输注，结果表明在这些条件下，通过肝葡萄糖-6-磷酸酶的绝对碳流量被极大抑制。1小时后，肝[UDP-葡萄糖]和[葡萄糖-6-磷酸]下降了50%-60%，且在整个实验过程中前者一直保持在低水平。相比之下，[葡萄糖-6-磷酸]在2小时时回升至初始值，并在随后的1小时内保持在该水平。我们对这些数据的解释如下。外源性葡萄糖除了作为肝葡萄糖-6-磷酸的前体之外，还会使后者从游离葡萄糖生成途径转向糖原合成途径。[UDP-葡萄糖]的下降与赫斯（《生物化学年度评论》1976年；45:167-189）提出的葡萄糖诱导的糖原合酶激活一致。然而，葡萄糖-6-磷酸浓度的先降后升序列构成了体内在葡萄糖-6-磷酸酶水平同时存在抑制作用的首个直接证据。
