Document Type

Grant

Publication Date

9-1-2014

Department

Chemistry

Abstract

In addition to the antihyperglycemic effects, metformin has shown to inhibit glycation of proteins, protecting their structure and function in diabetes-associated complications. Formation of nonenzymatic advanced glycation end products was studied in the presence of antidiabetic agent metformin and its structural analogs: phenformin, buformin, guanidinobutyric acid, and aminoguanidine. MGO was used as the glycating agent while aminoguanidine was used as the known antiglycation agent. The rate and extent of fluorescence generated upon formation of the in vitro cross-linked BSA by MGO was studied using the excitation wavelength of 330 nm. The fluorescence emission spectra of cross-linked BSA gave maximum values at 410 – 430 nm, regardless of the inhibitors used. The fluorescence generation was measured at 410 nm at 30°C over 96 hours at two concentrations of metformin and its analogs. At 10 mM MGO, no inhibition was exhibited and metformin and its structural analogs seemed to promote glycation. At 30 mM MGO, metformin (81%) and phenformin (93%) showed reduced glycation at 0.8 mM. At 30 mM MGO, buformin (51%), guanidinobutyric acid (69%), and metformin (94%) showed reduced glycation at 2.0 mM. At 100 mM, phenformin (86%) and metformin (84%) showed reduced glycation at 0.8 mM. At 100 mM, metformin (85%) was found to be the only drug to reduce glycation at 2.0 mM. Neither metformin nor its structural analogs proved to be as effective as aminoguanidine. The molecular weights of the cross-linked products determined by SDS PAGE indicated the formation of intramolecular cross-linked proteins in the presence of metformin and its structural analogs. SDS PAGE also confirmed that metformin and its analogs studied here were not potent antiglycation agents in vitro.

Content Notes

Research Report, Final Report Form

First Advisor

Myoung Lee

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