Female rats do not exhibit free fatty acid-induced insulin resistance
Female rats do not exhibit free fatty acid-induced insulin resistance
复制标题
DOI：
10.2337/diabetes.51.6.1907
复制
发表时间：
2002-06-01
期刊：
影响因子：
7.7
通讯作者：
Olefsky, J
中科院分区：
文献类型：
--
作者：
Hevener, A;Reichart, D;Olefsky, J
已经充分描述了过度的脂质代谢可以在动物和人类中引起胰岛素抵抗，并且这已经被认为是人类胰岛素抵抗和2型糖尿病发展的致病因素。最近，我们已经表明，在120分钟的血糖-高胰岛素钳夹过程中静脉注射脂肪乳剂（liposyn）导致胰岛素作用和脂肪酸移位酶（FAT/CD 36）骨骼肌蛋白表达显着减少。在回顾文献后，很明显，基本上所有过去的研究，包括我们自己的研究，都是在雄性动物中进行的。因此，为了确定是否存在脂肪诱导的胰岛素抵抗的性别决定因素，我们评估了游离脂肪酸（FFA）升高对雌性大鼠胰岛素作用的影响。在这里，我们报告说，血浆FFA浓度的四倍升高诱导胰岛素刺激的葡萄糖处置率降低40%，胰岛素刺激的骨骼肌胰岛素底物受体-1（IRS-1）磷酸化下降30%，IRS-1相关的磷脂酰肌醇（PI）3-激酶活性下降48%，肌肉FAT/CD 36蛋白表达下降50%。与此形成鲜明对比的是，我们没有发现FFA升高对雌性动物的胰岛素抵抗、IRS-1/PI 3-激酶或FAT/CD 36蛋白水平的影响。我们的研究结果表明，雌性动物的保护，从脂质诱导的胰岛素作用的减少。
It is well described that excessive lipid metabolism can cause insulin resistance in both animals and humans, and this has been implicated as a causative factor in the development of insulin resistance and type 2 diabetes in humans. Recently, we have shown that intravenous lipid emulsion (liposyn) infusion during a 120-min englycemic-hyperinsulinemic clamp led to significant reductions in insulin action and fatty acid translocase (FAT/CD36) skeletal muscle protein expression. After reviewing the literature, it became evident that essentially all past studies, including our own, were conducted in male animals. Therefore, to determine whether there were sex determinants of fat-induced insulin resistance, we assessed the impact of free fatty acid (FFA) elevation on insulin action in female rats. Here, we report that a fourfold elevation in plasma FFA concentration induced a 40% reduction in the insulin-stimulated glucose disposal rate, a 30% decline in insulin-stimulated skeletal muscle insulin substrate receptor-1 (IRS-1) phosphorylation, a 48% decrease in IRS-1-associated phosphatidylinositol (PI) 3-kinase activity, and a 50% reduction in muscle FAT/CD36 protein expression in male rats. In striking contrast, we found no effect of FFA elevation to cause insulin resistance, changes in IRS-1/PI 3-kinase, or FAT/CD36 protein levels in female animals. Our findings indicate that female animals are protected from lipid-induced reductions in insulin action.