Usami M, Seino Y, Taminato T, Seno M, Koh G, Ohno M, Ikeda M, Imura H
Division of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, Japan.
Life Sci. 1988;42(2):129-36. doi: 10.1016/0024-3205(88)90676-5.
The effect of a specific alpha 2-adrenergic antagonist 2-[2-(4,5-dihydro-1.H-imidazol-2-yl)-1-phenyl-ethyl] pyridine dihydrochloride sesquihydrate (DG5128), on the glucose output by epinephrine and/or glucagon was studied using the perfused rat liver. The administration of DG5128 alone did not affect the glucose output. However, DG5128 produced a significant inhibition of the increased glucose output when induced by 10(-6) M epinephrine alone or 10(-6) M epinephrine plus 1.4 x 10(-10) M glucagon. There were no significant changes of the glucose output by 1.4 x 10(-10) M or 7.0 x 10(-11) M glucagon alone. On the other hand, addition of 1 mU/ml insulin to the perfusate suppressed the 7.0 x 10(-11) M glucagon-induced glucose output, but failed to decrease the 1.4 x 10(-10) M glucagon effect. DG5128 suppressed further the glucagon (7.0 x 10(-11) M)-induced increase of glucose output in the presence of insulin. These results suggest that DG5128 produces a hypoglycemic effect partly through an inhibition of the increased hepatic glucose output elicited by epinephrine and glucagon.
使用灌注大鼠肝脏研究了一种特异性α2 - 肾上腺素能拮抗剂2 - [2 - (4,5 - 二氢 - 1.H - 咪唑 - 2 - 基) - 1 - 苯基 - 乙基]吡啶二盐酸盐倍半水合物（DG5128）对肾上腺素和/或胰高血糖素引起的葡萄糖输出的影响。单独给予DG5128不影响葡萄糖输出。然而，当由单独的10(-6) M肾上腺素或10(-6) M肾上腺素加1.4 x 10(-10) M胰高血糖素诱导时，DG5128对增加的葡萄糖输出产生显著抑制。单独使用1.4 x 10(-10) M或7.0 x 10(-11) M胰高血糖素时，葡萄糖输出无显著变化。另一方面，向灌注液中添加1 mU/ml胰岛素可抑制7.0 x 10(-11) M胰高血糖素诱导的葡萄糖输出，但未能降低1.4 x 10(-10) M胰高血糖素的作用。在存在胰岛素的情况下，DG5128进一步抑制了胰高血糖素（7.0 x 10(-11) M）诱导的葡萄糖输出增加。这些结果表明，DG5128部分通过抑制肾上腺素和胰高血糖素引起的肝脏葡萄糖输出增加而产生降血糖作用。
