Stevenson A, Merali Z, Kacew S, Singhal R L
Toxicology. 1976 Nov-Dec;6(3):265-75. doi: 10.1016/0300-483x(76)90029-9.
The effects of chronic oral ingestion of lead in doses ranging from 20-80 ppm were compared with those seen after the subacute exposure of rats to a 10 mg/kg daily dose of the heavy metal for 7 days. Irrespective of the treatment regimen used, lead treatment significantly increased the activities of renal pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase. The observed enhancement of kidney gluconeogenic enzymes in chronically treated animals was associated with a stimulation of the adenylate cyclase-cyclic AMP system, a rise in blood blucose and urea as well as a depression in hepatic glycogen and serum immunoreactive insulin (IRI) levels. In contrast, subacute exposure to lead failed to significantly alter cyclic AMP metabolism and the concentrations of liver glycogen, blood glucose, serum urea or IRI. Whwereas the insulinogenic index (the ratio of serum IRI to blood glucose concentration) was markedly suppressed in chronically treated rats, this ratio remained within normal limits following subacute exposure to the heavy metal. However, a marked decrease in the insulinogenic index was observed in subacutely treated rats 15 min after the administration of a glucose load. The data provide evidence to show that increased glucose synthesis as well as suppressed pancreatic function may be responsible for lead-induced disturbances in glucose homeostasis.
将大鼠慢性口服摄入剂量为20 - 80 ppm的铅的影响，与大鼠亚急性暴露于每日10 mg/kg重金属剂量7天之后的影响进行了比较。无论采用何种治疗方案，铅处理均显著增加了肾丙酮酸羧化酶、磷酸烯醇丙酮酸羧激酶、果糖1,6 -二磷酸酶和葡萄糖6 -磷酸酶的活性。在长期接受治疗的动物中观察到的肾糖异生酶增强，与腺苷酸环化酶 - 环磷酸腺苷系统的刺激、血糖和尿素升高以及肝糖原和血清免疫反应性胰岛素（IRI）水平降低有关。相比之下，亚急性暴露于铅未能显著改变环磷酸腺苷代谢以及肝糖原、血糖、血清尿素或IRI的浓度。虽然长期接受治疗的大鼠中胰岛素生成指数（血清IRI与血糖浓度之比）显著降低，但在亚急性暴露于重金属后该比值仍保持在正常范围内。然而，在亚急性处理的大鼠给予葡萄糖负荷15分钟后，观察到胰岛素生成指数显著下降。这些数据提供了证据表明，葡萄糖合成增加以及胰腺功能受抑制可能是铅诱导的葡萄糖稳态紊乱的原因。
