GLYCOGEN SYNTHASE PHOSPHATES IN DIABETES

糖原合成酶磷酸盐在糖尿病中的作用

• 批准号: 3151616
• 负责人: BALWANT SINGH KHATRA
• 金额: $ 11.31万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-07-01 至 1986-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3151616
• 关键词: carbohydrate metabolism; enzyme structure; enzyme substrate; glycogen synthase; phosphatase inhibitor; phosphorylation; radiotracer; striated muscles

The activation of synthase (D to I conversion) has been shown to be slow in several tissues from fasted and diabetic animals. This may due to (a) lower or inhibited phosphoprotein phosphatase activity, (b) existance of modified (highly phosphorylated) forms of synthase which are poor substrates or, (c) both. Results of present investigation show that glycogen synthase from normal, epinephrine treated and diabetics rabbit skeletal muscle has 2.4, 3.85 and 3.91 moles of phosphate per mole subunit, respectively. The distribution of phosphate in the trypsin sensitive and trypsin insensitive phosphorylation regions in normal, epinephrine treated and diabetic rabbits was 0.95 and 1.4; 2.09 and 1.75 and 1.08 and 2.84, moles respectively, thus suggesting that cAMP-independent syntase kinase plays an important role in the phosphorylation of synthase in normal and diabetic rabbits. It is proposed to further investigate the in vivo phosphate content and distribution of phosphate in the trypsin sensitive and trypsin insensitive regions of synthase in skeletal muscle of fasted, insulin treated normal and insulin treated diabetic rabbits. The results of the study will be used to prepare purified 32P synthases with a phosphate content similar to that found in these rabbits. These 32P-synthase preparations will then be used to investigate the phosphoprotein phosphatase activities in normal, diabetic and insulin treated rabbits. In addition, the levels of phosphoprotein phosphatase inhibitor 1 and 2 will also be studies in these muscle extracts. The investigation will give further insight into the regulation of glycogen synthase and phosphoprotein phosphatase activity in rabbit skeletal muscle.

合成酶的激活（D到I的转化）已经被证明是缓慢的， 禁食和糖尿病动物的几种组织。 这可能是由于（a）较低或 抑制的磷蛋白磷酸酶活性，（B）修饰的（高度） 磷酸化）形式的合成酶，其是不良底物，或（c）两者。 目前的研究结果表明， 肾上腺素治疗组和糖尿病组兔骨骼肌分别为2.4、3.85和3.91 每摩尔亚基的磷酸盐摩尔数。 的分布 胰蛋白酶敏感磷酸化和胰蛋白酶不敏感磷酸化 正常兔、肾上腺素治疗兔和糖尿病兔的脑电图面积分别为0.95和1.4; 2.09分别为1.75、1.08和2.84摩尔，因此表明， cAMP非依赖性合成酶激酶在磷酸化中起重要作用 正常和糖尿病兔的合成酶。 拟进一步 研究体内磷酸盐含量和磷酸盐分布， 骨骼肌合成酶的胰蛋白酶敏感区和胰蛋白酶不敏感区 空腹、胰岛素治疗的正常和胰岛素治疗的糖尿病兔。 的 研究结果将用于制备纯化的32 P脱氢酶， 磷酸盐含量与这些兔子中发现的相似。 这些32 P-合酶 然后将使用制备物来研究磷蛋白磷酸酶 正常、糖尿病和胰岛素治疗的家兔中的活性。 此外该 磷蛋白磷酸酶抑制剂1和2的水平也将在 这些肌肉提取物 调查将进一步了解 糖原合成酶和磷蛋白磷酸酶活性的调节 兔骨骼肌

项目成果

Subunit structure and properties of the glycogen-bound phosphoprotein phosphatase from skeletal muscle.

骨骼肌糖原结合磷蛋白磷酸酶的亚基结构和特性。

• 发表时间: 1986
• 期刊: The Journal of biological chemistry
• 作者: Khatra,BS

Purification of glycogen-bound high-molecular-weight phosphoprotein phosphatase from rabbit skeletal muscle.

从兔骨骼肌中纯化糖原结合的高分子量磷蛋白磷酸酶。

• DOI: 10.1016/0076-6879(88)59037-7
• 发表时间: 1988
• 期刊: Methods in enzymology
• 作者: Khatra,BS