INTERNATIONAL CONFERENCE ON GASTROENTERIC BIOLOGY

国际胃肠生物学会议

• 批准号: 3434610
• 负责人: JOHN H WALSH
• 金额: $ 0.3万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-30 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3434610
• 关键词: drug related diabetes mellitus; excretion; gastrointestinal absorption /transport; ion transport; liver cells; liver circulation; meeting /conference /symposium; membrane permeability; streptozotocin

The uptake of chemicals into hepatocytes and subsequent excretion into bile are mediated by membrane transport systems. These carriers are involved in removing endogenous and exogenous toxic chemicals from the blood thereby facilitating elimination from the body. A number of studies have indicated that exposure to numerous toxicants and several disease states can affect these transport systems. The long-term objectives of this research include isolation and characterization of the molecular entities involved in the transport of organic anions out of the hepatocyte across the canalicular membrane and into bile. In vivo data indicate that insulin-dependent diabetes alters the biliary clearance of several xenobiotic chemicals, but the mechanisms responsible for these changes are unknown. Because diabetes increases the synthesis and enterohepatic recirculation of bile acids and bile acids are known to interact with the organic anions transporter, the proposed studies will examine transporter kinetics in bile canalicular-enriched plasma membrane vesicles that are isolated from liver of normal, streptozotocin-induced diabetic without insulin treatment and insulin-treated diabetic rats. This project will answer the specific hypotheses: 1) is the decreased biliary bicarbonate in excretion due to altered properties of the canalicular chloride/bicarbonate transporter and 2) is the altered organic anion excretion due to an allosteric interaction of bile acids with the canalicular anion transporter. A proposed kinetic model describing the interactions between bile acids and organic anions will be refined. These kinetic studies of canalicular transport in diabetic rats will facilitate comprehension of the complex processes of hepatic elimination and may assist in the development of more effective drug therapy for diabetic patients.

化学物质对肝细胞的摄取和随后的 排泄成胆汁的是由膜运输系统介导的。 这些载体参与去除内源和外源性 血液中的有毒化学物质，从而促进消除 从身体。 许多研究表明暴露 对于众多有毒物质和几种疾病状态会影响这些 运输系统。 这项研究的长期目标 包括分离和表征分子实体 参与从肝细胞中运输有机阴离子 穿过大口腔膜，进入胆汁。 体内数据 表明胰岛素依赖性糖尿病会改变胆道 几种异生物化学物质的清除率，但是机制 负责这些变化是未知的。 因为糖尿病 增加胆汁的合成和肠肝循环 已知酸和胆汁酸会与有机阴离子相互作用 提议的研究将检查转运蛋白动力学 在胆管富含质膜囊泡中 从正常，链蛋白酶诱导的糖尿病的肝脏中分离出来 没有胰岛素治疗和胰岛素治疗的糖尿病大鼠。 这 项目将回答具体假设：1） 由于特性的改变，胆汁碳酸氢盐在排泄中 口腔氯化物/碳酸氢盐转运蛋白和2）是改变的 由于胆汁的变构相互作用，有机阴离子排泄 带有管子阴离子转运蛋白的酸。 提出的动力学 描述胆汁酸与有机物之间相互作用的模型 阴离子将被完善。 这些动力学研究 糖尿病大鼠的运输将有助于理解 肝消除的复杂过程，可能有助于 为糖尿病患者开发更有效的药物治疗。