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The role of adenosine 3′:5′-cyclic monophosphate in the regulation of insulin release. Properties of islet-cell adenosine 3′:5′-cyclic monophosphate phosphodiesterase

机译:腺苷3'的作用:5'-环状单磷酸盐在胰岛素释放的调节中。胰岛细胞腺苷3'的性质:5'-环状二磷酸磷酸二酯酶

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p1. An assay has been developed with sufficient sensitivity for determination of the adenosine 3′:5′-cyclic monophosphate diesterase activity in islets of Langerhans, and has been used to investigate the response of the enzyme to various agents which are known to affect insulin release. 2. The subcellular distribution of the enzyme in islets of Langerhans prepared from guinea-pig pancreas was investigated and over 70% of the activity present in the original homogenate was recovered in the supernatant fraction. 3. Gel filtration of the activity present in the supernatant fraction on Sephadex G-200 gave a single peak of activity with an apparent molecular weight of 200000. The phosphodiesterase activity in the peak fraction showed two apparent iKsubm/sub/i values for adenosine 3′:5′-cyclic monophosphate (cyclic AMP) of 3μm and 30μm, suggesting the presence of two activities. The pH optimum of the activity with the low iKsubm/sub/i value was 8.7. 4. Theophylline, caffeine, 3-isobutyl-1-methylxanthine (SC-2964), glibenclamide, tolbutamide, xylitol and leucine were inhibitors of the activity with the low iKsubm/sub/i value; imidazole and arginine stimulated the activity, and glucose and diazoxide were without significant effect. 5. It is suggested that the agents theophylline, caffeine, SC-2964, glibenclamide, tolbutamide, leucine and imidazole may alter the intracellular concentration of cyclic AMP in islets of Langerhans by affecting the cyclic AMP phosphodiesterase activity in islet cells and in this way may affect insulin release./p
机译:> 1。已经开发了一种测定,具有足够的灵敏度来测定腺苷3':兰氏菌胰岛中的5'-环状单磷酸二磷酸酯酶活性,并用于研究酶对已知胰岛素释放的各种试剂的响应。 2.研究了从豚鼠胰腺制备的含叶犬胰岛胰岛酶的亚细胞分布,并在上清液级分中回收原始匀浆中存在的70%的活性。 3.凝胶过滤在Sephadex G-200上的上清液部分中存在的活性产生了单一的活性,表观分子量为200000。峰值级分中的磷酸二酯酶活性显示出两种表观 k <亚> m < /亚氨酸3'的值3':5'-环状单磷酸(环状amp)为3μm和30μm,表明存在两种活性。具有低 K m 值的活性的pH值为8.7。 4.茶碱,咖啡因,3-异丁基-1-甲基黄嘌呤(SC-2964),Glibenclamide,甲丁酰胺,木糖醇和亮氨酸是具有低 K m 的活性的抑制剂价值;咪唑和精氨酸刺激了活性,葡萄糖和二酰胺没有显着效果。有人建议通过影响胰岛细胞的环状AMP磷酸二酯酶活性,通过影响胰岛细胞中的环状AMP磷酸二酯酶活性来改变胰岛素,甲酰胺,甲磺酰胺,亮氨酸和咪唑的蛋白质,咖啡因,SC-2964,Glibenclamide,甲醛酰胺,亮氨酸和咪唑可以通过影响胰岛细胞中的环状AMP磷酸二酯酶活性来改变朗格汉斯胰岛的细胞内浓度影响胰岛素释放。

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