Increase in 3-deoxyglucosone levels in diabetic rat plasma. Specific in vivo determination of intermediate in advanced Maillard reaction.

Abstract

A specific assay of 3-deoxyglucosone (3-DG) was developed in our laboratory to help elucidate the relationship between advanced Maillard reaction and diabetic complications. 3-DG is known as a highly reactive intermediate of the reaction in vitro and a precursor of advanced glycosylation end products such as pyrraline and pentosidine, which have been previously detected in vivo. 3-DG was converted to a stable compound, 2-(2,3,4-trihydroxybutyl)-benzo[g]quinoxaline, by reacting with 2,3-diaminonaphthalene. Since the derivative had a characteristic UV spectrum, it was determined at 268 nm by high performance liquid chromatography. This method was sensitive enough to detect 10 ng/ml (61.7 nM) of 3-DG in vitro. A slight modification to this method allowed in vivo detection of small amounts of 3-DG. Plasma free 3-DG levels were significantly higher in streptozotocin-induced diabetic rats compared with controls (918 +/- 134 nM versus 379 +/- 69 nM, p < 0.001) and were suppressed with the administration of aminoguanidine, an inhibitor of Maillard reaction. Plasma pyrraline levels in diabetic rats also increased in parallel with elevated 3-DG levels but were only marginally suppressed by administration of aminoguanidine. Our results indicate that 3-DG is present in vivo under normal conditions and that its level increases in diabetic subjects. Determination of 3-DG represents a good tool to predict development and progression of diabetic complications and to assess the efficiency of inhibitors to Maillard reaction.