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首页> 外文期刊>Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) >Multiple Drug Resistance Associated with Function of ABC-Transporters in Diabetes Mellitus: Molecular Mechanism and Clinical Relevance
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Multiple Drug Resistance Associated with Function of ABC-Transporters in Diabetes Mellitus: Molecular Mechanism and Clinical Relevance

机译:糖尿病中与ABC转运蛋白功能相关的多种耐药性:分子机制和临床意义

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摘要

ATP-binding cassette (ABC) transporters are involved in a variety of physiological processes such as lipid metabolism, ion homeostasis and immune functions. A large number of these proteins have been causatively linked to rare and common human genetic diseases including familial high-density lipoprotein deficiency, retinopathies, cystic fibrosis, diabetes and cardiomyopathies. Furthermore, genetic variations in ABC transporter genes and deregulated expression patterns significantly contribute to drug resistance in human cancer and pancreatic beta cells and alter the pharmacokinetic properties of a variety of drugs. Up-to-date 15 ABC transporters have been identified in human pancreatic beta cells, however only a few of them are identified to date as proteins/genes associated with multidrug resistance (MDR) in diabetes mellitus. Prominent members include the multidrug resistance protein 1 (MRP1/ABCC1), sulfonylurea receptor 1 (SUR1/ABCC8), the multi drug transporter TAP2 and member of the ATP-binding cassette transporter subfamily A (ABCA1). ABCC8 is a subunit of the pancreatic beta-cell K(ATP) channel and plays a key role in the regulation of glucose-induced insulin secretion. Although the physiological role of these transporters to MDR is not yet fully understood, they play an important role in the blood-membrane barrier in pancreatic beta cells. The aim of this article is to provide an overview and to present few examples of drug treatment in MDR in diabetes mellitus associated with function of ABC-transporters
机译:ATP结合盒(ABC)转运蛋白参与多种生理过程,例如脂质代谢,离子稳态和免疫功能。这些蛋白质中的许多已与罕见和常见的人类遗传病因果相关,包括家族性高密度脂蛋白缺乏症,视网膜病,囊性纤维化,糖尿病和心肌病。此外,ABC转运蛋白基因的遗传变异和表达模式失调显着促进了人类癌症和胰腺β细胞的耐药性,并改变了多种药物的药代动力学特性。在人类胰腺β细胞中已鉴定出最新的15种ABC转运蛋白,但是迄今为止,仅有少数几种被鉴定为与糖尿病多药耐药性(MDR)相关的蛋白质/基因。突出的成员包括多药抗性蛋白1(MRP1 / ABCC1),磺酰脲受体1(SUR1 / ABCC8),多药物转运蛋白TAP2和ATP结合盒转运蛋白亚家族A(ABCA1)的成员。 ABCC8是胰腺β细胞K(ATP)通道的一个亚基,在调节葡萄糖诱导的胰岛素分泌中起关键作用。尽管尚未完全理解这些转运蛋白对MDR的生理作用,但它们在胰腺β细胞的血膜屏障中起着重要作用。本文的目的是提供概述,并提供一些与ABC转运蛋白功能相关的糖尿病MDR药物治疗的实例

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