通过高葡萄糖对有机的运输商的监管
Martin Steinbüchel1, Johannes Menne1, Rita Schröter1
1Experimental Nephrology, Department of Internal Medicine D, University Hospital Münster, 48149 Münster, Germany.
International journal of molecular sciences
|September 28, 2023
概括
高葡萄糖刺激有机阴离子载体 (OCTs) 和多药物和毒素挤出蛋白 (MATEs),增加它们的活性和表达. 这可能会在早期糖尿病中增强甲型胺的吸收和阴离子分泌.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 有机离子体运输体 (OCTs) 和多药物和毒素挤出蛋白 (MATEs) 运输内源和外源的有机离子体,包括神经递质,毒素和像甲胺这样的药物.
- 这些载体对于通过肝脏和脏分泌有机酸盐至关重要,调节它们的全身度.
- 葡萄糖是一种关键的能量来源和信号分子,血液中的水平在生理和病理生理状态下波动.
研究的目的:
- 研究高葡萄糖度对有机阴离子载体 (OCT) 和多药物和毒素挤出蛋白 (MATE) 的活性和表达的影响.
- 探索葡萄糖诱导的载体调节的潜在机制,包括对mRNA和蛋白质表达的影响以及mTOR信号传递的作用.
- 评估这些变化的潜在影响在糖尿病和甲福林的药理动力学背景下.
主要方法:
- 稳定表达hOCT1,hOCT2或hMATE1的人类胚胎细胞在高葡萄糖 (16.7毫米) 或控制 (5.6毫米) 度下进行化48小时.
- 通过评估最大速度 (Vmax) 和基质亲和力来测量载体活性.
- 量化了mRNA和蛋白质表达水平,并评估了mTOR抑制 (Torin-1) 的作用. 使用曼尼托尔控制了度效应.
主要成果:
- 高葡萄糖显著刺激hOCT1,hOCT2和hMATE1的活性 (增加Vmax),而不会改变基质亲和力.
- 这种刺激与运输器mRNA的表达增加有关,对于hOCT2,血膜蛋白的表达增加.
- mTOR抑制抑制了葡萄糖诱导的输送器刺激. 在糖尿病患者的脏中观察到增加hOCT2mRNA的趋势.
结论:
- 用高葡萄糖 (16.7毫米) 进行48小时的化,可以增强有机阴离子载体的活性和表达.
- 这种高葡萄糖诱导的刺激,可能由mTOR信号介导,可能导致细胞吸收甲福尔的增加,并在早期糖尿病中增加有机离子体的分泌.
- 这些发现突出了糖尿病可能影响药物处置和内源性化合物清除的潜在机制.
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