Leitner J W, Kline T, Carel K, Goalstone M, Draznin B
Department of Medicine, Veterans Affairs Medical Center and the University of Colorado Health Sciences Center, Denver 80220, USA.
Endocrinology. 1997 May;138(5):2211-4. doi: 10.1210/endo.138.5.5240.
Incubation of 3T3-L1 fibroblasts with insulin (10 nM or 100 nM) for 24 or 48 hours resulted in a significant increase in the amount of farnesylated p21Ras with a concomitant increase in the amount of GTP-loaded p21Ras. Cells preincubated with 100 nM insulin for 24 or 48 hours exhibited further 5-8 fold increases in p21Ras.GTP loading in response to an acute (10 minute) challenge with either insulin, EGF, or IGF-1. Effects of hyperinsulinemia were completely abolished by the presence of 1 microM alpha-hydroxyfarnesylphosphonic acid, a potent inhibitor of farnesyltransferase. These novel observations indicate that hyperinsulinemia increases the cellular pool of farnesylated p21Ras and thereby potentiates activation of p21Ras by growth factors.
将3T3-L1成纤维细胞与胰岛素（10 nM或100 nM）孵育24或48小时，导致法尼基化的p21Ras量显著增加，同时GTP负载的p21Ras量也增加。用100 nM胰岛素预孵育24或48小时的细胞，在受到胰岛素、表皮生长因子（EGF）或胰岛素样生长因子-1（IGF-1）的急性（10分钟）刺激后，p21Ras.GTP负载进一步增加5 - 8倍。1 microM的α-羟基法尼基膦酸（一种有效的法尼基转移酶抑制剂）的存在完全消除了高胰岛素血症的影响。这些新发现表明，高胰岛素血症增加了法尼基化p21Ras的细胞池，从而增强了生长因子对p21Ras的激活作用。
