Purrello F, Gullo D, Buscema M, Pezzino V, Vigneri R, Goldfine I D
Cattedra di Endocrinologia e Patologia Costituzionale, University of Catania, Italy.
Diabetologia. 1988 Jun;31(6):385-9. doi: 10.1007/BF02341508.
The effect of the oral antidiabetic agent metformin on insulin regulation of glycogen metabolism, tyrosine-aminotransferase activity, and [1-14C]aminoisobutyric acid uptake was studied in H4IIE cultured rat hepatoma cells. Metformin enhanced both basal (from 0.213 +/- 0.016 to 0.262 +/- 0.024 nmol/mg protein, p less than 0.01) and insulin stimulated [3H] glucose incorporation into glycogen in a time-dependent and dose-dependent manner. A small effect of metformin was seen at 1 mumol/l, and its greatest effects were obtained at 10 mumol/l. At the same concentrations, metformin did not influence basal tyrosine-aminotransferase activity but it potentiated insulin stimulated tyrosine-aminotransferase activity (+29.2 +/- 1.4%, p less than 0.01) and prevented the loss of tyrosine-aminotransferase responsiveness to insulin in H4IIE cells desensitised by a previous exposure to insulin. In contrast, metformin had no effect on basal or insulin-stimulated [1-14C]aminoisobutyric acid uptake. Over the concentrations of metformin that enhanced insulin action in H4IIE cells, the drug had no significant effect on insulin binding to its receptor. These studies suggest, therefore, that metformin may influence cellular metabolism by potentiating certain insulin actions through mechanisms that may be beyond insulin receptor binding.
在H4IIE培养的大鼠肝癌细胞中研究了口服抗糖尿病药物二甲双胍对胰岛素调节糖原代谢、酪氨酸转氨酶活性及[1-14C]氨基异丁酸摄取的影响。二甲双胍以时间和剂量依赖性方式增强基础状态（从0.213±0.016增加至0.262±0.024 nmol/mg蛋白质，p<0.01）及胰岛素刺激的[3H]葡萄糖掺入糖原的过程。在1μmol/L时可见二甲双胍有较小作用，在10μmol/L时作用最大。在相同浓度下，二甲双胍不影响基础酪氨酸转氨酶活性，但可增强胰岛素刺激的酪氨酸转氨酶活性（增加29.2±1.4%，p<0.01），并防止先前暴露于胰岛素而脱敏的H4IIE细胞中酪氨酸转氨酶对胰岛素反应性的丧失。相反，二甲双胍对基础或胰岛素刺激的[1-14C]氨基异丁酸摄取无影响。在增强H4IIE细胞中胰岛素作用的二甲双胍浓度范围内，该药物对胰岛素与其受体的结合无显著影响。因此，这些研究提示，二甲双胍可能通过可能超出胰岛素受体结合的机制增强某些胰岛素作用来影响细胞代谢。
