Liu R H, Mizuta M, Kurose T, Matsukura S
Third Department of Internal Medicine, Miyazaki Medical College. Miyazaki, Japan.
Int J Obes Relat Metab Disord. 2002 Mar;26(3):318-26. doi: 10.1038/sj.ijo.0801924.
To clarify the mechanism by which insulin resistance develops in obesity, Zucker fatty rats (ZFR) and lean litter mates (ZLR) were temporally subjected to oral glucose tolerance tests (OGTT) at 6 and 15 weeks of age.
As candidates for causative factors of insulin resistance, plasma leptin, free fatty acids (FFA) and tumor necrosis factor (TNF)-alpha levels were evaluated.
There was no difference in the body weight between the two groups at 6 weeks of age, but ZFR were significantly heavier than ZLR at 15 weeks of age. At 6 weeks of age, blood glucose levels and area under the curve of glucose (AUCg) during OGTT were not significantly different between the two groups, while plasma insulin levels and area under the curve of insulin (AUCi) in the ZFR group were significantly higher than those in the ZLR group. At 15 weeks of age, the blood glucose levels and AUCg as well as plasma insulin levels and AUCi in the ZFR group during OGTT were significantly higher than those in the ZLR group. The ratio of fasting insulin to glucose in the ZFR group was significantly higher than that in the ZLR group at 6 and 15 weeks of age. Peripheral and portal plasma leptin and FFA levels were significantly higher in ZFR than ZLR both at 6 weeks and 15 weeks of age. Meanwhile, at 6 weeks, plasma TNF-alpha levels and expression of TNF-alpha protein in subcutaneous and visceral fat tissues were similar in both groups; however at 15 weeks, these were significantly higher in the ZFR group than the ZLR group.
These results suggest that FFA rather than TNF-alpha may play an important role in early events involved in the development of insulin resistance and TNF-alpha accelerates insulin resistance together with FFA in the later stage.
为阐明肥胖状态下胰岛素抵抗产生的机制，对祖克肥胖大鼠（ZFR）及其瘦体型同窝大鼠（ZLR）在6周龄和15周龄时进行了口服葡萄糖耐量试验（OGTT）。
评估血浆瘦素、游离脂肪酸（FFA）和肿瘤坏死因子（TNF）-α水平作为胰岛素抵抗致病因素的可能性。
两组在6周龄时体重无差异，但ZFR在15周龄时显著重于ZLR。6周龄时，两组在OGTT期间的血糖水平和葡萄糖曲线下面积（AUCg）无显著差异，而ZFR组的血浆胰岛素水平和胰岛素曲线下面积（AUCi）显著高于ZLR组。15周龄时，ZFR组在OGTT期间的血糖水平、AUCg以及血浆胰岛素水平和AUCi均显著高于ZLR组。ZFR组在6周龄和15周龄时空腹胰岛素与葡萄糖的比值显著高于ZLR组。ZFR在6周龄和15周龄时外周和门静脉血浆瘦素和FFA水平均显著高于ZLR。同时，6周时，两组血浆TNF-α水平以及皮下和内脏脂肪组织中TNF-α蛋白的表达相似；然而在15周时，ZFR组显著高于ZLR组。
这些结果表明，在胰岛素抵抗发生的早期事件中，FFA而非TNF-α可能起重要作用，而在后期TNF-α与FFA共同加速胰岛素抵抗。
