He Ling
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Trends Pharmacol Sci. 2020 Nov;41(11):868-881. doi: 10.1016/j.tips.2020.09.001. Epub 2020 Sep 28.
Metformin can improve patients' hyperglycemia through significant suppression of hepatic glucose production. However, up to 300 times higher concentrations of metformin accumulate in the intestine than in the circulation, where it alters nutrient metabolism in intestinal epithelial cells and microbiome, leading to increased lactate production. Hepatocytes use lactate to make glucose at the cost of energy expenditure, creating a futile intestine-liver cycle. Furthermore, metformin reduces blood lipopolysaccharides and its initiated low-grade inflammation and increased oxidative phosphorylation in liver and adipose tissues. These metformin effects result in the improvement of insulin sensitivity and glucose utilization in extrahepatic tissues. In this review, I discuss the current understanding of the impact of metformin on systemic metabolism and its molecular mechanisms of action in various tissues.
二甲双胍可通过显著抑制肝糖生成来改善患者的高血糖状况。然而，二甲双胍在肠道中的蓄积浓度比在循环系统中高300倍，它在肠道中会改变肠上皮细胞和微生物群的营养代谢，导致乳酸生成增加。肝细胞利用乳酸生成葡萄糖，却要消耗能量，从而形成了一个无效的肠-肝循环。此外，二甲双胍可降低血液中的脂多糖及其引发的低度炎症，并增加肝脏和脂肪组织中的氧化磷酸化。这些二甲双胍的作用可改善肝外组织的胰岛素敏感性和葡萄糖利用。在本综述中，我将讨论目前对二甲双胍对全身代谢影响及其在各种组织中的分子作用机制的理解。
