Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocin-induced diabetic rats

• Published in: Acta pharmacologica Sinica Vol. 32; no. 7; pp. 956 - 966
• Main Authors: Zhang, Lu-lu, Lu, Liang, Jin, Shi, Jing, Xin-yue, Yao, Dan, Hu, Nan, Liu, Li, Duan, Ru, Liu, Xiao-dong, Wang, Guang-ji, Xie, Lin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2011; Nature Publishing Group
• Subjects: Animals; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Biomedical and Life Sciences; Biomedicine; Cerebral Cortex - metabolism; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Gene Expression; Hippocampus - metabolism; Immunology; Internal Medicine; Intestinal Mucosa - metabolism; Kidney - metabolism; Liver - metabolism; Male; Medical Microbiology; mRNA水平; Original; original-article; Pharmacology/Toxicology; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; Vaccine; 糖尿病大鼠; 糖蛋白; 组织特异性; 罗丹明123; 聚合酶链反应; 诱导; 链脲佐菌素; P-glycoprotein; diabetes mellitus; insulin; ABC superfamily transporter; rhodamine 123; P-GP gene
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2011.33

Aim： To investigate the changes of expression and function of P-glycoprotein （P-GP） in cerebral cortex, hippocampus, liver, intestinal mucosa and kidney of streptozocin-induced diabetic rats. Methods： Diabetic rats were prepared via a single dose of streptozocin （65 mg/kg, ip）. Abcbl/P-GP mRNA and protein expression levels in tissues were evaluated using quantitative real time polymerase chain reaction （QRT-PCR） analysis and Western blot, respectively. P-GP function was investigated via measuring tissue-to-plasma concentration ratios and body fluid excretion percentages of rhodamine 123. Results： In 5- and 8-week diabetic rats, Abcbla mRNA levels were significantly decreased in cerebral cortices and intestinal mucosa, but dramatically increased in hippocampus and kidney. In liver, the level was increased in 5-week diabetic rats, and decreased in 8-week diabetic rats. Abcblb mRNA levels were increased in cerebral cortex, hippocampus and kidney, but reduced in liver and intestinal mucosa in the diabetic rats. Western blot results were in accordance with the alterations ofAbcbla mRNA levels in most tissues examined. P-GP activity was markedly decreased in most tissues of diabetic rats, except kidney tissues. Conclusion： Alterations in the expression and function of Abcbl/P-GP under diabetic conditions are tissue specific, Abcbl specific and diabetic duration-dependent.