MEMBRANE TRANSPORT REGULATION IN HEPATOCYTES

拟议的研究将解决离子传输的变化。 参与肝细胞葡萄糖代谢的调节。 很明显，离子传输的变化是一个重要的部分 细胞对糖调节激素的反应和对 底物进入的改变。因为它的核心作用 肝脏在葡萄糖代谢中的相互作用研究 膜转运、激素刺激与代谢 肝细胞的调节将具有特殊的相关性 糖尿病病理生理学。此外，这样的研究将有 更广泛地适用于各种类似的流程 上皮细胞，尤其是肾脏。 将解决以下问题： 1.底物递送-细胞对丙氨酸/钠的调节 运输：很明显，细胞在以下情况下会失去钾 丙氨酸进入增加。我们将定义 外排途径，确定触发K外流的信号， 并探讨该途径在糖异生中的作用。 回应。 2.胰岛素-Na/H交换的作用：已知胰岛素 刺激某些组织的Na-H交换以及对K的吸收 肌肉和肝脏细胞。我们将调查Na-H 肝细胞中的交换是开启的，并探索其作用 转运蛋白在调节其他胰岛素效应中的作用。 3.肾上腺素能药--蛋白激酶C和钙的作用： 我们将确定蛋白激酶C在介导 α-肾上腺素能药物的转运效应。对K的影响 将研究运输和Na/H交换的可能性 刺激将被探索。

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.