Department of Internal Medicine, Division of Endocrinology, Metabolism and Diabetes, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
Horm Metab Res. 2010 Aug;42(9):632-6. doi: 10.1055/s-0030-1255033. Epub 2010 Jun 17.
Metformin is reported to ameliorate inflammation in diabetic patients. The effect of metformin on lipopolysaccharide-induced nitric oxide production was studied by using RAW 264.7 macrophage-like cells. The action of metformin was analyzed by dividing lipopolysaccharide signaling into the MyD88-dependent and -independent pathways. Metformin significantly reduced the expression of an inducible type of nitric oxide synthase and inhibited lipopolysaccharide-induced nitric oxide production. On the other hand, metformin did not inhibit lipopolysaccharide-induced tumor necrosis factor-alpha production. The expression levels of interferon-beta protein and mRNA, which is a key molecule in MyD88-independent pathway, were significantly inhibited by metformin. Compound C, a specific AMP-activated protein kinase inhibitor, did not affect the inhibitory action of metformin. Metformin was suggested to inhibit lipopolysaccharide-induced nitric oxide production via inhibition of interferon-beta production in MyD88-independent pathway. Metformin might exhibit an anti- inflammatory action on diabetic complications as well as the antidiabetic action.
二甲双胍据报道可改善糖尿病患者的炎症。本研究通过 RAW 264.7 巨噬样细胞探讨了二甲双胍对脂多糖诱导的一氧化氮产生的影响。将二甲双胍的作用通过 MyD88 依赖性和非依赖性途径进行划分来进行分析。二甲双胍显著降低诱导型一氧化氮合酶的表达并抑制脂多糖诱导的一氧化氮产生。另一方面，二甲双胍不抑制脂多糖诱导的肿瘤坏死因子-α产生。干扰素-β蛋白和 mRNA 的表达水平，干扰素-β是 MyD88 非依赖性途径的关键分子，也被二甲双胍显著抑制。特定的 AMP 激活蛋白激酶抑制剂 Compound C 并不影响二甲双胍的抑制作用。二甲双胍通过抑制 MyD88 非依赖性途径中干扰素-β的产生来抑制脂多糖诱导的一氧化氮产生。二甲双胍可能除了具有抗糖尿病作用外，还对糖尿病并发症具有抗炎作用。
