Radziuk J, Pye S
Diabetes and Metabolism Research Unit, Ottawa Hospital, 1053 Carling Avenue, Ottawa, Ontario, Canada K1Y 4E9.
Diabetes Metab Res Rev. 2001 Jul-Aug;17(4):250-72. doi: 10.1002/dmrr.217.
Hepatic glycogen is replenished during the absorptive period postprandially. This repletion is prompted partly by an increased hepatic uptake of glucose by the liver, partly by metabolite and hormonal signals in the portal vein, and partly by an increased gluconeogenic flux to glycogen (glyconeogenesis). There is some evidence that the direct formation of glycogen from glucose and that formed by gluconeogenic pathways is linked. This includes: (i) the inhibition of all glycogen synthesis, in vivo, when gluconeogenic flux is blocked by inhibitors; (ii) a dual relationship between glucose concentrations, lactate uptake by the liver and glycogen synthesis (by both pathways) which indicates that glucose sets the maximal rates of glycogen synthesis while lactate uptake determines the actual flux rate to glycogen; (iii) the decrease of both gluconeogenesis and glycogen synthesis by the biguanide, metformin; and (iv) correlations between increased gluconeogenesis and liver glycogen in obese patients and animal models. The degree to which the liver extracts portal glucose is not entirely agreed upon although a preponderance of evidence points to about a 5% extraction rate, following meals, which is dependent on a stimulation of glucokinase. This enzyme may be linked to the expression of other enzymes in the gluconeogenic pathway. Perivenous cells in the liver may induce additional gluconeogenesis in the periportal cells by increasing glycolytically produced lactate. A number of potential mechanisms therefore exist which could link glycogen synthesis from glucose and gluconeogenic substrate.
肝糖原在餐后吸收期得以补充。这种补充部分是由肝脏对葡萄糖摄取增加所促使，部分是由门静脉中的代谢物和激素信号引起，还有部分是由于糖异生通量增加至糖原（糖原异生）。有一些证据表明，由葡萄糖直接形成的糖原与通过糖异生途径形成的糖原是相关联的。这包括：（i）当糖异生通量被抑制剂阻断时，体内所有糖原合成均受到抑制；（ii）葡萄糖浓度、肝脏对乳酸的摄取与糖原合成（通过两条途径）之间的双重关系，这表明葡萄糖设定了糖原合成的最大速率，而乳酸摄取决定了糖原合成的实际通量速率；（iii）双胍类药物二甲双胍可使糖异生和糖原合成均减少；（iv）肥胖患者和动物模型中糖异生增加与肝糖原之间的相关性。尽管大量证据表明餐后肝脏对门静脉葡萄糖的提取率约为5%，且这依赖于葡萄糖激酶的刺激，但对于肝脏提取门静脉葡萄糖的程度尚未完全达成共识。这种酶可能与糖异生途径中其他酶的表达相关。肝脏的肝静脉周围细胞可能通过增加糖酵解产生的乳酸来诱导门静脉周围细胞产生额外的糖异生。因此，存在许多潜在机制可将由葡萄糖和糖异生底物合成糖原联系起来。
