Age-associated changes of insulin action on the hydrolysis of diacylglycerol generated from phosphatidic acid
Age-associated changes of insulin action on the hydrolysis of diacylglycerol generated from phosphatidic acid
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DOI：
10.1016/j.cbpb.2006.03.005
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发表时间：
2006-07-01
影响因子：
2.2
通讯作者：
Giusto, N. M.
中科院分区：
文献类型：
--
作者：
Pasquare, S. J.;Salvador, G. A.;Giusto, N. M.
在大鼠大脑皮层突触体中研究了胰岛素对二酰甘油（DAG）降解作用的年龄相关变化。在成年（4 月龄）和老年（28 月龄）大鼠的大脑皮层 (CC) 突触体中研究了 DAG 生成单酰基甘油 (MAG) 和水溶性产物（WSP、甘油加甘油-3-磷酸）的过程。此外，在同一组动物中评估了猪胰岛素和酪氨酸磷酸化的作用。在本研究中，我们证明 WSP 生成量与年龄相关的增加伴随着未改变的 MAG 水平。在二酰基甘油脂肪酶（DAG 脂肪酶）抑制剂 RHC-80267 存在的情况下，与成年大鼠膜相比，在老年大鼠的 CC 突触体中观察到对 MAG 产生的抑制作用较低。在这些实验条件下，WSP 的形成仅在老化的膜中减少。在成年动物中，胰岛素在较长的孵育时间（30 分钟）内会刺激 MAG 和 WSP 的形成，而对老年动物则具有抑制作用。胰岛素加钒酸盐（作为酪氨酸磷酸酶抑制剂）在短孵育时间内抑制 MAG 产生，而在长时间孵育的老年动物中观察到相同的效果。胰岛素加钒酸盐在成年和老年动物中在孵育 30 分钟时刺激 WSP 形成。我们的结果表明，与成年大鼠相比，胰岛素对老年大鼠 CC 突触体中外源 PA 产生的 MAG 和 WSP 的调节存在差异。 (c) 2006 Elsevier Inc. 保留所有权利。
Age-related changes in insulin action on diacylglycerol (DAG) degradation was studied in rat cerebral cortex synaptosomes. The generation of monoacylglycerol (MAG) and water soluble products (WSP, glycerol plus glycerol-3-phosphate) from DAG was studied in cerebral cortex (CC) synaptosomes from adult (4-month-old) and aged (28-month-old) rats. Additionally, the effect of porcine insulin and tyrosine phosphorylation was evaluated in the same group of animals. In this study we demonstrate that the age-related increase in WSP generation was accompanied by unmodified MAG levels. In the presence of diacylglycerol lipase (DAG lipase) inhibitor, RHC-80267, a lower inhibitory effect on MAG production was observed in CC synaptosomes from aged rats with respect to that in adult membranes. Under these experimental conditions, WSP formation was only diminished in aged membranes. Insulin stimulated MAG and WSP formation at long incubation times (30 min) in adult animals, while it had an inhibitory effect in aged animals. Insulin plus vanadate (as tyrosine-phosphatase inhibitor) inhibited MAG production at short incubation times whereas the same effect was observed in aged animals at long times of incubation. WSP formation was stimulated by insulin plus vanadate both in adult and aged animals at 30 min of incubation. Our results show that insulin differentially modulates MAG and WSP production from exogenous PA in CC synaptosomes from aged rats compared with adult rats. (c) 2006 Elsevier Inc. All rights reserved.