Nordlie R C, Alvares F L, Sukalski K A
Biochim Biophys Acta. 1982 Nov 24;719(2):244-50. doi: 10.1016/0304-4165(82)90095-2.
Glucose uptake/production was studied as a function of varied glucose loads in isolated perfused livers from glucagon-treated alloxan-diabetic rats. Uptake of D-[U-14C]glucose was seen at all levels studied - 9.5-71 mM. In studies with unlabelled D-glucose carried out in the absence of 3-mercaptopicolinate, livers of diabetic rats showed a net production of glucose with perfusate glucose levels less than 22 mM. Above this level, these livers exhibited a time- and concentration-dependent net uptake of glucose for a period of 20-30 min. When 4 mM 3-mercaptopicolinate, which inhibited gluconeogenesis from endogenous substrates, was included in perfusates, a continuous net uptake of unlabelled glucose was observed at all levels above 4 mM. This lowering of the null-point, cross-over glucose concentration was shown to relate mechanistically to the observed reduction in steady-state hepatic glucose 6-phosphate level produced by mercaptopicolinate. The need for supplemental mechanisms of glucose utilization by high Km hepatic enzyme(s) operative in the virtual absence of insulin-dependent glucokinase also is indicated by these observations and by kinetic analysis.
在胰高血糖素处理的四氧嘧啶糖尿病大鼠的离体灌注肝脏中，研究了葡萄糖摄取/生成与不同葡萄糖负荷的关系。在所研究的所有葡萄糖水平（9.5 - 71 mM）下均观察到D-[U-¹⁴C]葡萄糖的摄取。在无3-巯基吡啶甲酸盐的情况下用未标记的D-葡萄糖进行的研究中，糖尿病大鼠肝脏在灌注液葡萄糖水平低于22 mM时显示出葡萄糖的净生成。高于此水平，这些肝脏在20 - 30分钟内表现出时间和浓度依赖性的葡萄糖净摄取。当灌注液中加入4 mM抑制内源性底物糖异生的3-巯基吡啶甲酸盐时，在高于4 mM的所有水平均观察到未标记葡萄糖的持续净摄取。这种零点、交叉葡萄糖浓度的降低在机制上与观察到的巯基吡啶甲酸盐引起的稳态肝葡萄糖6-磷酸水平降低有关。这些观察结果和动力学分析也表明，在几乎没有胰岛素依赖性葡萄糖激酶的情况下，需要由高Km肝酶发挥作用的补充葡萄糖利用机制。
