Decreased blood levels of glyoxalase I and diabetic complications

Abstract

The formation of Advanced Glycation Endproducts (AGEs) has been found to play a role in the development of diabetic symptoms. Production of methylglyoxal (MG), a highly cytotoxic and crosslinking aldehyde, is elevated among patients with type 2 diabetes mellitus (T2DM) and is a precursor to AGEs. The ubiquitous glyoxalase system is one of several defense mechanisms involved in MG metabolism and the protection against the production of AGEs. The system is a complex of two enzymes: glyoxalase I (GloI) that converts MG and reduced glutathione (GSH) to S-lactoylglutathione which is converted to D-lactic acid by glyoxalase II, regenerating GSH in the process. The malfunctioning of the glyoxalase system results in the accumulation of MG. The present study was performed to explore the relationship between the decreased activity of GloI and the complications associated to T2DM. The activities of the GloI, GloII and the concentration of GSH were measured in blood samples of 203 volunteers: 75 controls, 60 non-insulino-dependent diabetes mellitus (NIDDM) individuals and 68 NIDDM patients with complications as follow: 18 with nephropathy, 15 with retinopathy, 15 with neuropathy and 20 with macroangiopathy. All individuals were from the northen region of Morocco. We also evaluated the relationships between GloI levels and the pathogenesis of micro- and macrovascular complications of diabetes. We found a significant decrease in the GloI activity and GSH levels in patients with diabetes compared to controls. GloI activity was further reduced in samples from diabetes patients with complications. The levels of GloI were markedly lower in blood samples from patients with nephropathy than in uncomplicated patients and normal subjects. In contrast, there was no significant change in the activity of GloII in NIDDM patients compared to controls. This study suggests that the low level of GloI activity in T2DM patients is most probably due to decreased level of GSH content and reflects the role of GloI enzyme in protecting T2DM patients from AGEs accumulation and further complications.