Metformin-d6 is intended for use as an internal standard for the quantification of metformin by GC- or LC-MS. Metformin is a biguanide with diverse biological activities.1,2,3,4 Metformin (250 mg/kg, i.p.) increases hepatic AMPK activity and reduces blood glucose by more than 50% in a liver kinase B1-dependent manner in mice fed normal and high-fat diets, respectively, and reduces blood glucose by 40% in ob/ob mice.2 It reduces weight gain, hepatic lipid droplet content, and total cholesterol, LDL cholesterol, and triglyceride levels in the plasma of diet-induced obese mice when administered at doses of 10 or 50 mg/kg per day.4 It also reverses increased hepatic triglyceride and apolipoprotein A5 levels, as well as hepatic steatosis, in a dose-dependent manner in an ob/ob mouse model of non-alcoholic fatty liver disease (NAFLD).5 Metformin (250 mg/kg) reduces tumor growth in an HCT116 p53-\- human colon cancer mouse xenograft model, but has no effect on HCT116 p53-\- tumors overexpressing recombinant S. cerevisiae Ndi1 NADH dehydrogenase, a single-subunit ortholog of the multi-subunit mammalian mitochondrial complex I.3 Formulations containing metformin have been used in the treatment of type 2 diabetes.
1.Viollet, B., Guigas, B., Garcia, N.S., et al.Cellular and molecular mechanisms of metformin: An overviewClin. Sci. (Lond.)122(6)253-270(2012) 2.Shaw, R.J., Lamia, K.A., Vasquez, D., et al.The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metforminScience3101642-1646(2005) 3.Wheaton, W.W., Weinberg, S.E., Hamanaka, R.B., et al.Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesisElife3:e02242(2014) 4.Kim, E.K., Lee, S.H., Jhun, J.Y., et al.Metformin prevents fatty liver and improves balance of white/brown adipose in an obesity mouse model by inducing FGF21.Mediators Inflamm.5813030(2016) 5.Lin, M.-J., Dai, W., Scott, M.J., et al.Metformin improves nonalcoholic fatty liver disease in obese mice via down-regulation of apolipoprotein A5 as part of the AMPK/LXRα signaling pathwayOncotarget8\(65)108802-108809(2017)