Begum N A, Datta A G
Indian Institute of Chemical Biology 4, Calcutta.
Mol Cell Biochem. 1992 Aug 18;113(2):93-103. doi: 10.1007/BF00231529.
Using rat hepatocytes we confirmed our previous results that glucagon and beta-adrenergic agonists increased the enzyme activity of alanine aminotransferase (AAT) and propranolol abolished their effects. Only the enzyme activity was measured and other parameters like quantity of the enzyme or activation due to modification were not looked for. As in perfusion experiment phenylephrine and phenoxybenzamine (alpha-agonist and alpha-antagonist respectively) also alpha-antagonist respectively) also increased the AAT activity in isolated rat hepatocytes and propranolol reversed these effects. The additive effect of glucagon and phenoxybenzamine on AAT was also persistent in hepatocyte system. Fructose-1:6-bisphosphatase (Fru-P2-ase), another key enzyme in gluconeogenic pathway, was elevated by glucagon and other beta-adrenergic agonists both in liver perfusion and isolated hepatocyte experiments and was brought back to the normal level by propranolol. In this case also only the enzyme activity was measured and no other parameters were looked for. Unlike AAT this enzyme was not stimulated by phenylephrine or phenoxybenzamine. But AAT and Fru-P2-ase activities were increased significantly by adenylate cyclase activators like fluoride or forskolin. Thus, it appears that the regulation of fru-P2-ase by glucagon is purely a b-receptor mediated process whereas AAT activation shows a mixed type of regulation where some well known alpha-agonist and antagonists are behaving as beta-agonists. Results further indicate the presence of phosphodiesterase in hepatocyte membrane which was stimulated by glucagon and brought back to the normal level by propranolol. The different adrenergic compounds stated above, not only modified the activity of the above two enzymes but also stimulated glucose production by hepatocytes from alanine which was in turn abolished by propranolol as well as amino oxyacetate (AOA), a highly specified inhibitor of AAT. This confirm the participation of AAT in gluconeogenesis from alanine in liver. Forskolin and fluoride also increased the glucose production from alanine and showed additive effects with glucagon, phenylephrine and phenoxybenzamine.
利用大鼠肝细胞，我们证实了之前的结果：胰高血糖素和β-肾上腺素能激动剂可增加丙氨酸转氨酶（AAT）的酶活性，而普萘洛尔可消除它们的作用。仅测量了酶活性，未探究其他参数，如酶的数量或修饰导致的激活情况。如同在灌注实验中一样，去氧肾上腺素和酚苄明（分别为α-激动剂和α-拮抗剂）在分离的大鼠肝细胞中也增加了AAT活性，普萘洛尔可逆转这些作用。胰高血糖素和酚苄明对AAT的相加作用在肝细胞系统中也持续存在。果糖-1:6-二磷酸酶（Fru-P2-ase）是糖异生途径中的另一种关键酶，在肝脏灌注和分离肝细胞实验中，胰高血糖素和其他β-肾上腺素能激动剂均可使其升高，普萘洛尔可使其恢复至正常水平。在此情况下同样仅测量了酶活性，未探究其他参数。与AAT不同，该酶不受去氧肾上腺素或酚苄明的刺激。但腺苷酸环化酶激活剂如氟化物或福斯高林可显著增加AAT和Fru-P2-ase的活性。因此，似乎胰高血糖素对Fru-P2-ase的调节纯粹是一个β受体介导的过程，而AAT的激活表现为一种混合类型的调节，一些知名的α-激动剂和拮抗剂表现得如同β-激动剂。结果进一步表明肝细胞膜中存在磷酸二酯酶，其受胰高血糖素刺激，普萘洛尔可使其恢复至正常水平。上述不同的肾上腺素能化合物不仅改变了上述两种酶的活性，还刺激肝细胞从丙氨酸生成葡萄糖，而普萘洛尔以及AAT的高度特异性抑制剂氨氧乙酸（AOA）均可消除这种作用。这证实了AAT参与肝脏中由丙氨酸进行的糖异生过程。福斯高林和氟化物也增加了从丙氨酸生成葡萄糖的量，并与胰高血糖素、去氧肾上腺素和酚苄明表现出相加作用。
