Rohner-Jeanrenaud F, Proietto J, Ionescu E, Jeanrenaud B
Diabetes. 1986 Dec;35(12):1350-5. doi: 10.2337/diab.35.12.1350.
The genetically obese fa/fa rat is glucose intolerant when tested in a conscious state after the spontaneous ingestion of a glucose solution. The aim of this study was to investigate the mechanism(s) underlying the abnormal oral glucose tolerance test of obese animals with the non-steady-state measurement of glucose turnover proposed by Steele et al. in 1968. Our results show that the total rate of glucose appearance is enhanced in obese compared with lean animals. This abnormality is not due to an increased gut glucose absorption but to a lack of suppression and even a transient stimulation of hepatic glucose production after the ingestion of glucose. The rate of glucose utilization by the obese animals is somewhat increased compared with controls or unchanged when expressed as glucose metabolic clearance rate, thus excluding this parameter from the factors contributing to the observed glucose intolerance. The results obtained with genetically obese rats agree with those reported for type II diabetes in humans. The observed defect of the obese group could be related to an abnormal regulation of insulin counterregulatory hormone(s) or of hepatic innervation as well as to other defects of hepatic glycogen handling.
基因肥胖的fa/fa大鼠在自发摄入葡萄糖溶液后处于清醒状态下进行测试时，存在葡萄糖不耐受情况。本研究的目的是利用Steele等人于1968年提出的非稳态葡萄糖周转率测量方法，探究肥胖动物口服葡萄糖耐量试验异常的潜在机制。我们的结果表明，与瘦动物相比，肥胖动物的葡萄糖出现总速率有所提高。这种异常并非由于肠道葡萄糖吸收增加，而是由于摄入葡萄糖后肝脏葡萄糖生成缺乏抑制甚至出现短暂刺激。与对照组相比，肥胖动物的葡萄糖利用率有所增加，或者以葡萄糖代谢清除率表示时保持不变，因此排除了该参数是导致观察到的葡萄糖不耐受的因素之一。基因肥胖大鼠获得的结果与人类II型糖尿病的报道结果一致。肥胖组观察到的缺陷可能与胰岛素对抗调节激素或肝脏神经支配的异常调节以及肝脏糖原处理的其他缺陷有关。
