Favreau L V, Schenkman J B
Department of Pharmacology, University of Connecticut Health Center, Farmington 06032.
Diabetes. 1988 May;37(5):577-84. doi: 10.2337/diab.37.5.577.
Monospecific polyclonal antibodies to five constitutive hepatic microsomal cytochromes P-450 were prepared. These antibodies were used to monitor alterations in the content of the enzymes in livers of diabetic male rats. Within 3 wk of onset of streptozocin-induced diabetes, immunodetectable levels of RLM3 and RLM5 were decreased by 85 and greater than 95%, respectively. Insulin treatment for 1 wk reversed the decline in these isozymes and restored RLM3 to 60% and RLM5 to 53% of levels found in the untreated rat. After a 2nd wk of therapy, these levels were returned to 86 and 92%, respectively. In contrast, the levels of RLM5b and RLM6 were elevated in diabetes 1.7- and 8-fold, respectively. Insulin treatment for 1 wk only slightly decreased the levels of RLM5b but completely reduced RLM6 levels to those seen in age-matched untreated rats. After the 2nd wk of insulin treatment, the level of RLM5b was almost completely restored to normal, with no additional change in the RLM6 level. The level of a fifth enzyme, RLM5a, was not markedly altered by diabetes or by insulin treatment. The results suggest there are at least three types of responses by constituents of the cytochrome P-450 population to diabetes: no change in the microsomal content, a rapid increase when insulin level declines and restoration when insulin is supplied, and a rapid decline when insulin level declines and a restoration by insulin treatment.
制备了针对五种组成型肝微粒体细胞色素P-450的单特异性多克隆抗体。这些抗体用于监测糖尿病雄性大鼠肝脏中这些酶含量的变化。在链脲佐菌素诱导的糖尿病发病3周内，可免疫检测到的RLM3和RLM5水平分别下降了85%和超过95%。胰岛素治疗1周可逆转这些同工酶的下降，使RLM3恢复到未治疗大鼠水平的60%，RLM5恢复到53%。治疗第二周后，这些水平分别恢复到86%和92%。相比之下，糖尿病时RLM5b和RLM6的水平分别升高了1.7倍和8倍。胰岛素治疗1周仅使RLM5b水平略有下降，但使RLM6水平完全降至年龄匹配的未治疗大鼠的水平。胰岛素治疗第二周后，RLM5b水平几乎完全恢复正常，RLM6水平无进一步变化。第五种酶RLM5a的水平在糖尿病或胰岛素治疗后无明显改变。结果表明，细胞色素P-450群体的成分对糖尿病至少有三种反应类型：微粒体含量无变化，胰岛素水平下降时迅速增加，胰岛素供应时恢复；胰岛素水平下降时迅速下降，胰岛素治疗时恢复。
