Physical exercise enhances protein kinase C δ activity and insulin receptor tyrosine phosphorylation in diabetes-prone Psammomys obesus
Physical exercise enhances protein kinase C δ activity and insulin receptor tyrosine phosphorylation in diabetes-prone Psammomys obesus
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DOI：
10.1016/s0026-0495(03)00154-9
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发表时间：
2003-08-01
影响因子：
9.8
通讯作者：
Meyerovitch, J
中科院分区：
文献类型：
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作者：
Heled, Y;Shapiro, Y;Meyerovitch, J
我们最近报道了在营养诱导的2型糖尿病的动物模型Psamomys obesus中，体育锻炼可以防止2型糖尿病的进展。在目前的研究中，我们表征了体育锻炼对蛋白激酶C增量(PKCDelta)活性的影响，作为体内胰岛素信号级联的中介。三组沙鼠接受为期4周的饮食方案：高能量饮食(HE/C)、高能量饮食和运动(HE/EX)或低能量饮食(LE/C)。HE/EX组无一只发生糖尿病，而HE/C组所有动物均发生糖尿病。在隔夜禁食后，与HE/C组相比，腹腔注射胰岛素(1U)后，HE/EX和LE/C组的血糖水平下降幅度更大。HE/EX和LE/C组胰岛素受体(IR)、胰岛素受体底物-1(IRS-1)和磷脂酰肌醇3激酶(PI3)的酪氨酸磷酸化水平显著高于HE/C组。最后，与HE/C组相比，HE/EX和LE/C组IR相关的PKC增量更高。HE/EX和LE/C组PKC Delta与IR的共沉淀高于HE/C组。因此，我们认为，4周的体育锻炼可以改善沙鼠的胰岛素信号反应，并伴随着PKCDelta和IR之间的直接联系。这一机制可能与运动对沙棘2型糖尿病的预防作用有关。(C)2003 Elsevier Inc.保留所有权利。
We recently reported that physical exercise prevents the progression of type 2 diabetes mellitus in Psammomys obesus, an animal model of nutritionally induced type 2 diabetes mellitus. In the present study we characterized the effect of physical exercise on protein kinase C delta (PKCdelta) activity, as a mediator of the insulin-signaling cascade in vivo. Three groups of Psammomys obesus were exposed to a 4-week protocol: high-energy diet (HE/C), high-energy diet and exercise (HE/EX), or low-energy diet (LE/C). None of the animals in the HE/EX group became diabetic, whereas all the animals in the HE/C group became diabetic. After overnight fast, intraperitoneal (IP) insulin (1U) caused a greater reduction in blood glucose levels in the HE/EX and LE/C groups compared to the HE/C group. Tyrosine phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and phosphatidylinositol 3 kinase (PI3 kinase) was significantly higher in the HE/EX and LE/C groups compared with the HE/C group. Finally, IR-associated PKCdelta was higher in the HE/EX and LE/C groups compared to the HE/C group. Coprecipitation of PKCdelta with IR was higher in the HE/EX and LE/C groups compared to the HE/C group. Thus, we suggest that 4 weeks of physical exercise results in improved insulin-signaling response in Psammomys obesus accompanied by a direct connection between PKCdelta and IR. We conclude that this mechanism may be involved in the preventive effect of exercise on type 2 diabetes mellitus in Psammomys obesus. (C) 2003 Elsevier Inc. All rights reserved.