MEMBRANE TRANSPORT REGULATION IN HEPATOCYTES

肝细胞的膜运输调节

• 批准号: 3876160
• 负责人: BRIAN J COHEN
• 金额: --
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3876160
• 关键词: diabetes mellitus; glucose metabolism; guinea pigs; hormone regulation /control mechanism; insulin; ion transport; laboratory rat; liver cells; membrane activity; sodium potassium exchanging ATPase

The proposed studies will address the changes in ion transport involved in the regulation of glucose metabolism in hepatocytes. It is clear that alterations in ion transport are an important part of the cell response to glucoregulatory hormones and to alterations in substrate entry. Because of the central role of the liver in glucose metabolism, the study of the interaction between membrane transport, hormonal stimulation and metabolic regulation in hepatocytes will have special relevance to the pathophysiology of diabetes. In addition, such studies will have more general relevance to similar processes in a variety of epithelia, particularly the kidney. The following issues will be addressed: 1. Substrate delivery- Cell adjustments to alanine/sodium contransport: It is clear that the cell loses potassium when increased alanine entry occurs. We will define the nature of the efflux pathway, determine the signal that triggers the K efflux, and explore the role of this pathway in the gluconeogenic response. 2. Insulin-The role of Na/H exchange: Insulin is known to stimulate Na-H exchange in some tissues as well as K uptake into muscle and liver cells. We will investigate whether Na-H exchange is turned on in hepatocytes and explore the role of this transporter in mediating other insulin effects. 3. Adrenergic agents-The roles of protein kinase C and calcium: We will establish the role of protein kinase C in mediating the transport effects of alpha adrenergic agents. The effects on K transport will be studied and the possibility that Na/H exchange is stimulated will be explored.

拟议的研究将解决离子运输的变化 参与肝细胞中葡萄糖代谢的调节。 很明显，离子转运的改变是一个重要的部分， 细胞对糖调节激素的反应， 基板进入的改变。 由于中央的作用， 肝脏在葡萄糖代谢中，相互作用的研究 膜转运、激素刺激和代谢 肝细胞中的调节将与 糖尿病的病理生理学 此外，这些研究将 更普遍的相关性，以类似的过程中的各种 上皮细胞，尤其是肾脏。 将讨论以下问题： 1. 底物递送-细胞对丙氨酸/钠的调节 共转运：很明显，细胞失去钾， 出现增加的丙氨酸进入。 我们将定义 外排途径，确定触发钾外排的信号， 并探索这一通路在致肿瘤中的作用， 反应 2. 胰岛素-Na/H交换的作用：已知胰岛素 刺激某些组织中Na-H交换以及K吸收进入 肌肉和肝细胞。 我们将调查Na-H是否 交换在肝细胞中打开，并探讨这一作用 转运蛋白介导其他胰岛素效应。 3. 肾上腺素能药物-蛋白激酶C和钙的作用： 我们将确定蛋白激酶C在介导细胞凋亡中的作用。 α肾上腺素能药物的转运作用。 对K的影响 运输将被研究，Na/H交换的可能性是 刺激将被探索。