ABC家族转运体与糖尿病

Diabetes and ATP-binding cassette transporters

糖尿病是一种常见的全身性慢性代谢疾病,其发病过程伴随着血糖、血脂和激素水平的失调,并由此引发高血脂、动脉粥样硬化、心肌病等并发症。ABCA,ABCB,ABCC,ABCG等ABC家族转运体有可能参与糖尿病及其并发症发病机制。如ABCA1和ABCG1促使细胞内的胆固醇泵出,进入高密度脂蛋白通路,减少巨噬细胞中的胆固醇沉积,防止巨噬细胞转化为泡沫细胞;ABCG5和ABCG8抑制肠道膳食中脂类吸收,并促进胆固醇通过胆汁排泄;表达在胰岛β细胞上的ABCC8作为钾通道的调节亚基控制胰岛素的释放,维持血糖平衡;ABCB1,ABCC1-ABCC5以及ABCG2是药物转运相关的外排蛋白,影响着其底物药物的体内过程,也参与体内内源性物质的转运。上述ABC家族转运体缺失或变异有可能诱发糖尿病及其并发症;而糖尿病状态下体内环境的变化也会改变这些ABC家族转运体表达与功能,进一步加剧了病情的发展。本文讨论了糖尿病及与之相关的四类ABC家族转运体,以期深入理解两者之间的相互作用,为糖尿病研究和治疗提供新思路。

Diabetes is a common systematic disease.It was reported that complications of diabetes such as hyperlipemia,atherosclerosis and cardiomyopathies might result from disorders of blood glucose,blood lipid and hormone homeostasis.It was reported that four subfamilies of the ATP-binding cassette(ABC)transporter such as ABCA,ABCB,ABCC and ABCG,play important roles in this modulation.ABCA1 and ABCG1 export excess cellular cholesterol into the HDL pathway,reduce cholesterol accumulation in macrophages and prevent from translation of macrophages into 'foam cells' in the artery wall.ABCG5 and ABCG8 limit absorption of dietary sterols in the intestine and promote cholesterol elimination from the body through hepatobiliary secretion.ABCC8,as a untypical transporter,regulates ATP-sensitive K+ channels in insulin-secreting pancreatic β cells to maintain the glucose homeostasis.ABCB1,ABCC1-ABCC5 and ABCG2 are common efflux transporters of drugs,that influence their substrates' physiological disposition.Mutations of these subfamilies of ABC transporters may induce diabetes and its complications.The function and expression of ABC transporters may be impaired under diabetes condition,in turn which intensify the diabetes and its complications.Here,the relationship between the diabetes and four subfamilies of ABC transporters is reviewed in order to provide some new ideas and new targets for the study of diabetes.