INHIBITORY EFFECT OF METFORMIN ON FORMATION OF ADVANCED GLYCATION END-PRODUCTS

To determine the inhibitory effect of metformin hydrochloride (MT) on advanced glycation end products (AGEs) and to compare MT's potency wit h that of aminoguanidine hydrochloride (AG), a high concentration of D -glucose (1.7 M) and 1 mM bovine serum albumin were incubated at 37 de grees C for 60 days with MT or AG (0 to 100 mM). AGEs were measured by competitive enzyme-linked immunosorbent assay with two kinds of polyc lonal antibodies for N-e-(carboxymethyl)lysine (CML) and nonspecific A GEs. To assess the inhibitory patterns of AGE formation by both agents , sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis was performed. MT significantly inhibited CML formation from 1 mM (MT:gluc ose molar ratio, 1:1700; 90 +/- 3.5% baseline) to 100 mM (MT:glucose m olar ratio, 1:17; 58 +/- 4.9% baseline). Both SDS-polyacrylamide gel e lectrophoresis patterns, including 100 mM AG and MT, showed similar at tenuation of broad bands in high molecular weight areas (>97.4 K) and increments of bands in low molecular weight areas (>66.2 K, less than or equal to 97.4 K) near native albumin compared with the findings wit hout inhibitors. These data indicate that MT has an antiglycative acti vity and potency similar to those of AG.