Manuel Keenoy B, Maggetto C, Malaisse W J
Laboratory of Experimental Medicine, Erasmus Medical School, Brussels Free University, Belgium.
Biochem Med Metab Biol. 1993 Aug;50(1):35-53. doi: 10.1006/bmmb.1993.1045.
In erythrocytes from diabetic rats the generation of radioactive metabolites from 3H- or 14C-labeled D-glucose occurs at a lower rate than in cells from control animals, while the total production of L-lactic acid is the same in both cell types. The radioisotopic anomaly is not corrected by agents causing phosphofructokinase activation and is not attributable to interference of metabolites generated from either glycogen or 2,3-diphospho-D-glycerate. It is mimicked by preincubating the erythrocytes at a high concentration of D-glucose and suppressed in diabetic rats treated with insulin in order to lower the blood glucose concentration prior to sacrifice. These findings suggest isotopic dilution of the 3H- or 14C-labeled tracer by endogenous unlabeled D-glucose. The influence of factors such as the concentration of erythrocytes in the incubation medium, the concentration of extracellular D-glucose, and the length of incubation upon radioactive metabolic variables is also compatible with the postulated phenomenon of isotopic dilution.
在糖尿病大鼠的红细胞中,3H或14C标记的D-葡萄糖产生放射性代谢物的速率低于对照动物细胞,而两种细胞类型中L-乳酸的总产量相同。引起磷酸果糖激酶激活的试剂无法纠正这种放射性同位素异常,且这并非归因于糖原或2,3-二磷酸-D-甘油酸产生的代谢物的干扰。通过在高浓度D-葡萄糖下预孵育红细胞可模拟这种情况,而在处死前用胰岛素治疗以降低血糖浓度的糖尿病大鼠中这种情况会受到抑制。这些发现表明内源性未标记的D-葡萄糖对3H或14C标记的示踪剂进行了同位素稀释。孵育介质中红细胞浓度、细胞外D-葡萄糖浓度以及孵育时间等因素对放射性代谢变量的影响也与假定的同位素稀释现象相符。