Nihon Bioresearch Inc., Hashima, Gifu 501-6251, Japan.
Biol Pharm Bull. 2010;33(6):963-70. doi: 10.1248/bpb.33.963.
In an acute treatment experiment, metformin (150, 300 mg/kg, per os (p.o.)) markedly reduced the consumption of a high-fat diet (HFD) (45 kcal% fat-containing diet) for 2 h after the HFD was given to the fasted male C57BL/6J (B6) mice. In addition, metformin at a higher dose increased plasma active glucagon-like peptide-1 (GLP-1) levels at 1 h after the HFD was given. On the other hand, pioglitazone (12 mg/kg, p.o.) slightly increased the food intake but did not affect active GLP-1 levels when given at 6 and 12 mg/kg, p.o. In a long-team experiment for 9 weeks, metformin treatment (0.25, 0.5% in the HFD) resulted in reduction of body weight gain and HFD intake. When wet weights of various body fat pads of each mouse were measured at 9 weeks after treatment, metformin markedly decreased these weights. However, pioglitazone treatment (0.01, 0.02% in the HFD) did not have obvious effects on these parameters. Oral glucose tolerance test was carried out after 20-h fasting at 4 weeks post-treatment. Whereas metformin treatment (0.25, 0.5%) markedly improved glucose intolerance, pioglitazone treatment (0.02%) slightly improved this parameter. At 9 weeks, both metformin and pioglitazone markedly improved hyperglycemia and hyperinsulinemia. Metformin treatment also improved hyperleptinemia, whereas pioglitazone was ineffective. These results indicate that metformin reduces body weight gain and improves glucose intolerance in HFD-induced obese diabetic B6 mice.
在一项急性治疗实验中，二甲双胍（150、300mg/kg，口服（p.o.））显著减少了禁食雄性 C57BL/6J（B6）小鼠在给予高脂肪饮食（HFD）后 2 小时对高脂肪饮食（HFD）的消耗。此外，二甲双胍在较高剂量时会增加 HFD 给予后 1 小时的血浆活性胰高血糖素样肽-1（GLP-1）水平。另一方面，吡格列酮（12mg/kg，p.o.）给药时，即使以 12mg/kg、p.o.的剂量给药，也仅略微增加食物摄入量，但不影响活性 GLP-1 水平。在 9 周的长期实验中，二甲双胍治疗（HFD 中 0.25、0.5%）导致体重增加和 HFD 摄入减少。治疗 9 周后测量每只小鼠各种体脂肪垫的湿重时，二甲双胍显著降低了这些重量。然而，吡格列酮治疗（HFD 中 0.01、0.02%）对这些参数没有明显影响。在治疗后 4 周进行 20 小时禁食后的口服葡萄糖耐量试验。二甲双胍治疗（0.25、0.5%）显著改善葡萄糖耐量，而吡格列酮治疗（0.02%）仅轻微改善该参数。在 9 周时，二甲双胍和吡格列酮均显著改善高血糖和高胰岛素血症。二甲双胍治疗还改善了高瘦素血症，而吡格列酮则无效。这些结果表明，二甲双胍可减轻体重增加并改善 HFD 诱导的肥胖糖尿病 B6 小鼠的葡萄糖不耐受。
