首页> 美国卫生研究院文献>Scientific Reports >Hyperglycemia and hyperlipidemia blunts the Insulin-Inpp5f negative feedback loop in the diabetic heart
【2h】

Hyperglycemia and hyperlipidemia blunts the Insulin-Inpp5f negative feedback loop in the diabetic heart

机译:高血糖和高血脂使糖尿病心脏的胰岛素-Inpp5f负反馈回路变钝

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

The leading cause of death in diabetic patients is diabetic cardiomyopathy, in which alteration of Akt signal plays an important role. Inpp5f is recently found to be a negative regulator of Akt signaling, while its expression and function in diabetic heart is largely unknown. In this study, we found that in both the streptozotocin (STZ) and high fat diet (HFD) induced diabetic mouse models, Inpp5f expression was coordinately regulated by insulin, blood glucose and lipid levels. Increased Inpp5f was inversely correlated with the cardiac function. Further studies revealed that Insulin transcriptionally activated Inpp5f in an Sp1 dependent manner, and increased Inpp5f in turn reduced the phosphorylation of Akt, forming a negative feedback loop. The negative feedback plays a protective role under diabetic condition. However, high blood glucose and lipid, which are characteristics of uncontrolled diabetes and type 2 diabetes, increased Inpp5f expression through activation of NF-κB, blunts the protective feedback. Thus, our study has revealed that Inpp5f provides as a negative feedback regulator of insulin signaling and downregulation of Inpp5f in diabetes is cardioprotective. Increased Inpp5f by hyperglycemia and hyperlipidemia is an important mediator of diabetic cardiomyopathy and is a promising therapeutic target for the disease.
机译:糖尿病患者的主要死亡原因是糖尿病性心肌病,其中Akt信号的改变起着重要的作用。最近发现Inpp5f是Akt信号的负调节剂,而其在糖尿病心脏中的表达和功能尚不清楚。在这项研究中,我们发现在链脲佐菌素(STZ)和高脂饮食(HFD)诱导的糖尿病小鼠模型中,Inpp5f的表达均受胰岛素,血糖和脂质水平的调节。 Inpp5f的增加与心脏功能成反比。进一步的研究表明,胰岛素以Sp1依赖性方式转录激活Inpp5f,而Inpp5f的增加反过来又降低了Akt的磷酸化,形成了负反馈环。负反馈在糖尿病情况下起保护作用。然而,高血糖和高血脂是不受控制的糖尿病和2型糖尿病的特征,通过激活NF-κB可以增加Inpp5f的表达,从而削弱了保护性反馈。因此,我们的研究表明,Inpp5f可作为胰岛素信号的负反馈调节剂,而Inpp5f在糖尿病中的下调具有心脏保护作用。高血糖和高血脂引起的Inpp5f升高是糖尿病性心肌病的重要介质,并且是该疾病的有希望的治疗靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号