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首页> 外文期刊>Endocrinology, Diabetes & Metabolism >The impact of acute rosiglitazone on insulin pharmacokinetics at the blood‐brain barrier
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The impact of acute rosiglitazone on insulin pharmacokinetics at the blood‐brain barrier

机译：急性罗格列酮对血脑屏障胰岛素药代动力学的影响

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Introduction CNS insulin levels are decreased and insulin receptor signalling is dampened in Alzheimer's disease (AD). Increasing CNS insulin levels through a variety of methods has been shown to improve memory. Indeed, medications routinely used to improve insulin resistance in type 2 diabetes are now being repurposed for memory enhancement. CNS insulin is primarily derived from the circulation, by an active transport system at the blood‐brain barrier (BBB). The goal of this study was to determine whether rosiglitazone (RSG), a drug used to improve insulin sensitivity in type 2 diabetes, could enhance insulin transport at the BBB, as a potential therapeutic for improving memory. Methods Using radioactively labelled insulin and the multiple‐time regression analysis technique, we measured the rate of insulin BBB transport and level of vascular binding in mice pretreated with vehicle or 10?μg RSG in the presence or absence of an insulin receptor inhibitor. Results Although we found acute RSG administration does not affect insulin transport at the BBB, it does restore BBB vascular binding of insulin in an insulin receptor–resistant state. Conclusions Acute RSG treatment does not alter insulin BBB transport in healthy mice but can restore insulin receptor binding at the BBB in an insulin‐resistant state.
机译：引言CNS胰岛素水平降低，并且在阿尔茨海默病（AD）中抑制了胰岛素受体信号传导。通过各种方法增加CNS胰岛素水平，已显示出改善记忆。实际上，常规用于改善2型糖尿病患者胰岛素抵抗的药物现在正在重新恢复记忆增强。 CNS胰岛素主要由血脑屏障（BBB）的活性运输系统来源于循环。本研究的目的是确定Rosiglitazone（RSG）是否是用于改善2型糖尿病患者的胰岛素敏感性的药物，可以增强BBB处的胰岛素输送，作为改善记忆的潜在治疗方法。方法采用放射性标记的胰岛素和多次回归分析技术，从而测量了在胰岛素受体抑制剂的存在或不存在的情况下用载体预处理的小鼠或10μgrsg的小鼠胰岛素BBB传输和血管结合水平。结果虽然我们发现急性RSG给药不影响BBB的胰岛素输送，但它确实在胰岛素受体状态下恢复胰岛素的BBB血管结合。结论急性RSG治疗不会改变健康小鼠中的胰岛素BBB传输，但可以在胰岛素抗性状态下恢复在BBB处的胰岛素受体结合。

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