Novel I1-imidazoline S43126 enhance insulin action in PC12 cells.
Novel I1-imidazoline S43126 enhance insulin action in PC12 cells.
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新型 I1-咪唑啉 S43126 增强 PC12 细胞中的胰岛素作用。
DOI：
10.1016/s1734-1140(11)70708-3
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Edwards,LincolnP
中科院分区：
文献类型：
--
作者：
Tesfai,Jerusalem;Crane,Louis;Baziard-Mouysset,Genevieve;Kennedy,Wentsworth;Edwards,LincolnP
I1-咪唑啉受体是治疗高血压和胰岛素抵抗（与2型糖尿病相关的主要疾病）药物开发的新靶点。在本研究中，我们研究了一种新的咪唑啉激动剂S43126对蛋白激酶B（PKB/Akt）和细胞外信号调节激酶（ERK 12）磷酸化的影响。我们进一步研究了S43126对胰岛素刺激的PKB和ERK磷酸化的影响。用不同剂量的S43126处理PC 12细胞（10-10至10-6 M）或胰岛素（10-10至10-6 M）或与胰岛素（10-6 M）和不同剂量的S43126联合治疗（10-6-10-11 M）处理10分钟。处理样品的蛋白质印迹分析显示，S43126使ERK 1/2和PKB磷酸化增加了5倍。胰岛素（10-6 M）和不同剂量的S43126（10-6-10-11 M）联合治疗以剂量和时间依赖性方式增强PKB和ERK 1/2的磷酸化，高于单独胰岛素的水平。用针对Nischarin（11-咪唑啉受体的小鼠同源物）的siRNA处理降低了组合处理后ERK和PKB的磷酸化。这些结果表明，S43126具有增强胰岛素作用的潜力，应进一步研究作为治疗胰岛素抵抗状态的可能候选药物。
The I1-imidazoline receptor is a novel target for drug development for hypertension and insulin resistance, major disorders associated with type 2 diabetes. In the present study, we examined the effects of a novel imidazoline agonist S43126, on phosphorylation of protein kinase B (PKB/Akt) and extracellular signal-regulated kinase (ERK1/2) in PC12 cells. We further examined the effects of S43126 on insulin stimulated PKB and ERK phosphorylation. PC12 cells were treated with varying doses of S43126 (10-10 to 10-6 M) or insulin (10-10 to 10-6 M) or combination treatment with insulin (10-6 M) and varying doses of S43126 (10-6-10-11 M) for 10 min. Western blot analysis of treated samples showed that S43126 increased both ERK1/2 and PKB phosphorylation by 5 fold. Combination treatment with insulin (10-6 M) and varying doses of S43126 (10-6-10-11 M) enhanced phosphorylation of PKB and ERK1/2 above the level of insulin alone, in a dose and time dependent manner. Treatment with siRNA against Nischarin (mouse homologue of I 1-imidazoline receptor) reduced the phosphorylation of both ERK and PKB following combination treatments. These results indicate that S43126 has the potential to augment insulin action and should be further studied as a possible candidate drug for the treatment of insulin resistance states.