Davidson M B
Metabolism. 1981 Mar;30(3):279-84. doi: 10.1016/0026-0495(81)90152-9.
To study the pathways involved and the effect of insulin on the autoregulation of hepatic glucose balance, isolated hepatocytes from normal, diabetic and treated diabetic rats were incubated with varying concentrations of glucose (100-400 mg/dl) with and without pyruvate (10 mM). New glucose production or utilization was calculated from the change in media glucose concentrations before and after incubation, new glycogenolysis by the change in tissue glycogen levels before and after incubation, net glycolysis by following the incorporation of glucose-C14 into lactate C14 and gluconeogenesis by the difference in glucose production in the presence and absence of pyruvate. Hepatocytes from control and insulin-treated animals manifested autoregulation of glucose balance. Glucose modulated the glycogen and glycolytic pathways but did not affect gluconeogenesis. In hepatocytes from diabetic rats, there was no autoregulation, tissue glycogen was unmeasurable both before and after incubation, glycolysis was markedly curtailed and gluconeogenesis was increased. It may be concluded that (1) glucose autoregulates its own production or utilization by modulating the glycogen and glycolytic pathways, (2) autoregulation is lost in severe diabetes leading to fasting hyperglycemia, and (3) insulin has a permissive effect on the autoregulation of glucose balance by maintaining the rate-limiting enzymes, glycogen synthase and glucokinase, so that glucose can exert its effect on these pathways.
为了研究相关途径以及胰岛素对肝脏葡萄糖平衡自动调节的影响，将来自正常、糖尿病和治疗后的糖尿病大鼠的分离肝细胞，在有和没有丙酮酸（10 mM）的情况下，与不同浓度的葡萄糖（100 - 400 mg/dl）一起孵育。根据孵育前后培养基中葡萄糖浓度的变化计算新的葡萄糖生成或利用，根据孵育前后组织糖原水平的变化计算新的糖原分解，通过追踪葡萄糖 - C14掺入乳酸 - C14来计算净糖酵解，并根据有无丙酮酸时葡萄糖生成的差异计算糖异生。来自对照和胰岛素治疗动物的肝细胞表现出葡萄糖平衡的自动调节。葡萄糖调节糖原和糖酵解途径，但不影响糖异生。在糖尿病大鼠的肝细胞中，不存在自动调节，孵育前后组织糖原均无法测量，糖酵解明显减少，糖异生增加。可以得出以下结论：（1）葡萄糖通过调节糖原和糖酵解途径自动调节其自身的生成或利用；（2）在严重糖尿病中自动调节丧失，导致空腹高血糖；（3）胰岛素通过维持限速酶糖原合酶和葡萄糖激酶，对葡萄糖平衡的自动调节具有允许作用，从而使葡萄糖能够对这些途径发挥作用。
