Mazière J C, Mazière C, Mora L, Gardette J, Salmon S, Auclair M, Polonovski J
Faculté de Médecine Saint-Antoine, UA 524 du CNRS, Paris, France.
Atherosclerosis. 1988 May;71(1):27-33. doi: 10.1016/0021-9150(88)90299-7.
The effect of the hypoglycemic biguanide drug Metformin was investigated after a 72 h pretreatment of human cultured fibroblasts. Metformin induced a moderate increase in low density lipoprotein binding, uptake and internalization (25% increase after treatment with 5 X 10(-4) M of drug). A decrease in sterol, fatty acid and triacyglycerol synthesis from sodium acetate was observed after pretreatment with the drug, with a dose-dependent effect in the range of 5 X 10(-5) to 5 X 10(-4) M (50% reduction of sterol synthesis after treatment with Metformin 5 X 10(-4) M). This effect was also observed in fibroblasts from a patient with homozygous familial hypercholesterolemia. Cholesterol esterification studied by incorporation of radiolabeled oleic acid was reduced by Metformin (40% of control after treatment with Metformin 5 X 10(-4) M) whereas incorporation into triacylglycerols was less impaired. These effects of Metformin on cholesterol metabolism were observed either in the presence or in the absence of low density lipoproteins. Moreover, Metformin also reduced cholesterol esterification in J774 monocyte-macrophage cells. Metformin also induced a decrease of hydroxymethylglutaryl coenzyme A reductase activity in cultured fibroblasts and a reduction of acyl-coenzyme A: cholesterol-O-acyltransferase activity in cultured fibroblasts and J774 cells.
在对人培养的成纤维细胞进行72小时预处理后，研究了降血糖双胍类药物二甲双胍的作用。二甲双胍使低密度脂蛋白的结合、摄取和内化适度增加（用5×10⁻⁴ M药物处理后增加25%）。在用该药物预处理后，观察到从醋酸钠合成固醇、脂肪酸和三酰甘油减少，在5×10⁻⁵至5×10⁻⁴ M范围内呈剂量依赖性效应（用5×10⁻⁴ M二甲双胍处理后固醇合成减少50%）。在一名纯合子家族性高胆固醇血症患者的成纤维细胞中也观察到了这种效应。通过掺入放射性标记油酸研究的胆固醇酯化被二甲双胍降低（用5×10⁻⁴ M二甲双胍处理后为对照的40%），而掺入三酰甘油的情况受损较小。二甲双胍对胆固醇代谢的这些作用在有或没有低密度脂蛋白的情况下均观察到。此外，二甲双胍还降低了J774单核巨噬细胞中的胆固醇酯化。二甲双胍还导致培养的成纤维细胞中羟甲基戊二酰辅酶A还原酶活性降低，以及培养的成纤维细胞和J774细胞中酰基辅酶A：胆固醇-O-酰基转移酶活性降低。
