We tested the hypothesis that metformin produces arterial dilatation indirectly, by directly exposing the endothelial surface, of an occluded test segment of the pig iliac artery in vivo, to test blood containing metformin or excess insulin, with and without the presence of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester hydrochloride. Such exposure to metformin 1 μg/mL caused the artery to dilate at constant pressure, and this was abolished when NG-nitro-L-arginine methyl ester hydrochloride was coadministered with metformin. The onset of dilatation occurred approximately 4 minutes after the commencement of endothelial exposure to metformin; this contrasts with the approximate 10 minutes required for a similar response to luminal hyperinsulinemia.
View Article and Find Full Text PDFBackground And Aim: This study was undertaken to test the hypothesis that hyperglycaemia induces the generation of reactive oxygen species (ROS) by mitochondria and that the oxidative stress thereby exerted is diminished by treatment with metformin. As a parameter of mitochondrial ROS formation, the activity of mitochondrial aconitase activity was determined using Goto-Kakizaki (GK) rats as model of type 2 diabetes.
Methods: In parallel with the development of diabetes (glucose, insulin), the generation of oxidative stress was determined in aortic tissue, heart and kidney of GK rats by measurement of lipid peroxides, oxidized proteins (carbonyl activity) and mitochondrial aconitase activity.
Curr Drug Targets Immune Endocr Metabol Disord
June 2003
Although a number of assessments disagree, the preponderance of the evidence indicates that the major therapeutic action of metformin in type 2 diabetes (DM2) is on the liver, and glucose production (EGP) in particular. At the level of this organ, the actions of metformin can be characterized as pleiotropic. The major questions addressed here are therefore: (i) the methodological aspects of the determination of glucose fluxes: when glucose production is not found to be elevated in type 2 diabetes, it is not surprising that little action of metformin on this flux is found.
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