TYROSINE PHOSPHATASES AND INSULIN RESISTANCE IN THE AGED

该项目旨在确定重要的磷酸酶， 使激活形式的胰岛素受体去磷酸化，从而 终止胰岛素作用的早期步骤。通过在层面上进行干预 在这些磷酸酶中，人们可以解决胰岛素抵抗的问题 在成熟期发病的糖尿病状态。 这些研究需要准备几种新的试剂和 蜂窝系统的优化。多肽/蛋白质的现代技术 使用化学、受体生物化学和哺乳动物细胞培养 胰岛素受体动力学研究取得成功 磷酸化/去磷酸化。合成了几种新的多肽 并测试了它们调节胰岛素受体活性的能力。其中 这两组酪氨酸修饰的多肽似乎特异性地 调节胰岛素受体激酶和酪氨酸磷酸酶活性。 这些研究为两个领域的研究提供了新的方向 胰岛素受体磷酸酶的鉴定和抑制，以及 胰岛素信号转导途径的其他方面的研究。我们的 长期目标是开发安全有效的治疗方法 治疗老年糖尿病患者的干预措施。

This project is aimed at identifying important phosphatases that dephosphorylate the activated form of the insulin receptor, thereby terminating the early steps in insulin action. By intervening at the level of these phosphatases one could approach the problem of insulin resistance in maturity onset diabetic states. These studies have required the preparation of several new reagents and optimization of cellular systems. Modern techniques in peptide/protein chemistry, receptor biochemistry and mammalian cell culture were used successfully to study the dynamics of insulin receptor phosphorylation/dephosphorylation. Several novel peptides were synthesized and tested for their ability to modulate insulin receptor activity. Among them two sets of tyrosine-modified peptides appeared to specifically regulate insulin receptor kinase and tyrosine phosphatase activities. These studies provide new directions for the research in both the identification and inhibition of insulin receptor phosphatase, as well as the study of other aspects of the insulin signal transduction pathway. Our long term goal is the development of safe and effective therapeutic interventions for the treatment of older patients with diabetes.