ADENYLATE CYCLASE-MODULATING MEDIATORS OF INSULIN

Plasma membranes prepared from pig liver incubated with insulin (50—300 μU/ml) resulted in the release of at least two insulin chemical mediators. They appeared to modulate the activity of adenylate cyclase in liver plasma membrances of pig. One of them was fraction 1 of insulin mediator (M. W. about 3700—4000 dalton) which markedly stimulated the activity of the enzyme, the other was fraction 2 of insulin mediator (M. W. about 1000 dalton) which inhibited the enzyme activity. The results showed that the inhibitor of fraction 2 generated was significantly higher than that of fraction 1 when the membranes were incubated with insulin of low concentration (50—100 μU/ml). On the other hand, the generation of stimulator of fraction 1 from plasma membranes incubated with insulin of high concentration (200 μU/ml) was higher than that of fraction 2. So the ratio of yield between two mediators produced from the membranes was dependent on the concentration of insulin added. The results also showed that the     

THE ROLE OF INSULIN MEDIATORS IN REGULATION OF cAMP AND LIPOGENESIS AS WELL AS IN DIABETES

Plasma membranes prepared from pig, mouse and rat liver incubated with insulin resulted in the release of at least two insulin chemical mediators. These mediators, identified as fractions 1 and 3, were found to inhibit cAMP level in response to lipolytic hormone and forskolin and to enhance lipogenesis in adipocytes of rat. Fractions 1 and 3 have been estimated to have molecular weights of 3700—4000 and 1000—1500 dalton, respectively. This initial report will focus on fraction 1.Interestingly, liver membranes from diabetic animals were found not to release mediators in the presence of insulin. However, following in vivo treatment of diabetic animals with insulin, the liver membranes appeared to restore its ability in generating chemical mediators in response to insulin.     

胰岛素介体的作用——调节腺苷酸环化酶的胰岛素介体

本文证明用胰岛素(50—300μu/ml)处理猪肝细胞膜后,从膜释放出不止一种的胰岛素化学介体。它们对肝细胞膜上的腺苷酸环化酶有调节作用。一种是介体组份1,分子量为3700—4000D,有直接促进该酶活性的作用;另一种是介体组份2,分子量为1000 D左右,表现出明显抑制该酶活性的作用。两种介体释放的比率与保温的激素浓度相关。当胰岛素在生理浓度下(50一100μu/ml)诱导产生介体组份2为主,而在高于生理浓度下(200—300μu/ml)则诱导产生介体组份1为主。介体组份1对肝细胞膜腺苷酸环化酶活性的作用表现出双相性,组份2对该酶活性仅出现单相作用。两种介体组份分别与Gpp(NH)p和福司可林(forskolin)合并作用表明,胰岛素介体可能作用于腺苷酸环化酶的GTP调节蛋白组份而调节该酶的活性。     

促进和抑制脂肪合成的胰岛素介体

猪肝细胞膜与猪胰岛素(50—300μU/ml)保温后,从膜上释放出一种分子量为3700D的物质,称为介体组份1,有促进大白鼠的脂肪细胞的脂肪合成作用。另一种分子量为1000D左右的物质,称为介体组份2,有抑制脂肪合成作用。两种介体释放的比率与保温的激素浓度、生物活性密切相关。用不同生物活性的胰岛素类似物处理猪肝细胞膜诱导介体释放,可得到上述用不同浓度激素处理的同样结果。进一步证明胰岛素介体的产生依赖于诱导激素的生物活性,而与激素及其类似物与受体的结合活力无关。     

胰岛素介体的功能——调节细胞的cAMP和脂肪合成及糖尿病的影响

本文报道用猪、小白鼠和大白鼠肝细胞质膜与胰岛素(100—150μU/ml)保温后,从膜至少释放两种胰岛素介体(Insulin mediator或Insulin chemical mediator),即组份1和组份3。它们能抑制脂解激素和福司可林(Forskolin)所刺激的脂肪细胞的cAMP形成及促进细胞的脂肪合成。组份1的分子量约为3700—4000,组份3约1000—1500dalton。组份1胰岛素介体为本文第一次报道的新发现的化合物。糖尿病小白鼠或大白鼠的肝细胞膜产生此种介体比正常动物的明显下降,但经体内注射胰岛素治疗后,则介体的释放可恢复正常。     

LIPOGENESIS STIMULATORY AND INHIBITORY ACTIVITIES OF THE INSULIN MEDIATORS

Incubating plasma membranes prepared from pig liver with varying concentrations of insulin (50—1000 μU/ml) resulted in the release of at least two insulin chemical mediators. One of them was fraction 1 of insulin mediator (M. W. 3700—4000 daltons) which had a significant lipogenesis-stimulatlug activity. The other was fraction 2 of insulin mediator (M. W. about 1000 daltons) which exhibited a lipogenesis-inhibitory activity.The ratio of yield between the two mediators produced from the membranes was not only dependent on the concentration but also on the potency of insulin and its analogs added. The result showed that there was more production of fraction 2 than fraction 1 with the inducer at low concentration (100 μU/ml), while the production of fraction 1 from the plasma membranes incubated with high concentration of insulin (300 μU/ml) was higher than fraction 2. On the other hand, insulin and its analogs which have different biological activities and receptor bindtng activities have been used t