Department of Physiology and Biophysics, Institute of Biomedical Sciences-I, University of São Paulo USP, São Paulo, SP, Brazil.
J Pineal Res. 2013 Sep;55(2):156-65. doi: 10.1111/jpi.12056. Epub 2013 Apr 9.
In aged rats, insulin signaling pathway (ISP) is impaired in tissues that play a pivotal role in glucose homeostasis, such as liver, skeletal muscle, and adipose tissue. Moreover, the aging process is also associated with obesity and reduction in melatonin synthesis from the pineal gland and other organs. The aim of the present work was to evaluate, in male old obese Wistar rats, the effect of melatonin supplementation in the ISP, analyzing the total protein amount and the phosphorylated status (immunoprecipitation and immunoblotting) of the insulin cascade components in the rat hypothalamus, liver, skeletal muscle, and periepididymal adipose tissue. Melatonin was administered in the drinking water for 8- and 12 wk during the night period. Food and water intake and fasting blood glucose remained unchanged. The insulin sensitivity presented a 2.1-fold increase both after 8- and 12 wk of melatonin supplementation. Animals supplemented with melatonin for 12 wk also presented a reduction in body mass. The acute insulin-induced phosphorylation of the analyzed ISP proteins increased 1.3- and 2.3-fold after 8- and 12 wk of melatonin supplementation. The total protein content of the insulin receptor (IR) and the IR substrates (IRS-1, 2) remained unchanged in all investigated tissues, except for the 2-fold increase in the total amount of IRS-1 in the periepididymal adipose tissue. Therefore, the known age-related melatonin synthesis reduction may also be involved in the development of insulin resistance and the adequate supplementation could be an important alternative for the prevention of insulin signaling impairment in aged organisms.
在老年大鼠中，胰岛素信号通路（ISP）在肝脏、骨骼肌和脂肪组织等对葡萄糖稳态起关键作用的组织中受损。此外，衰老过程还与肥胖和松果腺及其他器官中褪黑素合成减少有关。本研究旨在评估补充褪黑素对老年肥胖 Wistar 雄性大鼠 ISP 的影响，分析大鼠下丘脑、肝脏、骨骼肌和附睾周围脂肪组织中胰岛素级联成分的总蛋白量和磷酸化状态（免疫沉淀和免疫印迹）。褪黑素在夜间通过饮用水给药 8 周和 12 周。食物和水的摄入以及空腹血糖保持不变。胰岛素敏感性在补充褪黑素 8 周和 12 周后分别增加了 2.1 倍。补充褪黑素 12 周的动物体重也减轻了。急性胰岛素诱导的分析 ISP 蛋白的磷酸化在补充褪黑素 8 周和 12 周后分别增加了 1.3 倍和 2.3 倍。除附睾周围脂肪组织中 IRS-1 的总蛋白量增加 2 倍外，所有研究组织中的胰岛素受体（IR）和 IRS-1、2 的总蛋白含量均保持不变。因此，已知的与年龄相关的褪黑素合成减少也可能与胰岛素抵抗的发展有关，适当的补充可能是预防老年机体胰岛素信号受损的重要方法。
