THE EFFECT OF DELTA-GLUCONOLACTONE, AN OXIDIZED ANALOG OF GLUCOSE, ONTHE NONENZYMATIC GLYCATION OF HUMAN AND RAT HEMOGLOBIN

Nonenzymatic glycation of proteins and oxidative stress are considered independent factors important in the development of the complications of diabetes but may be interrelated by the process of autoxidative gl ycation. This pathway involves monosaccharide autoxidation to a reacti ve ketoaldehyde analogue and subsequent reaction with protein to form a ketoimine adduct. This study demonstrates that delta-gluconolactone (delta-GL), an oxidised analogue of glucose, is st potent glycating ag ent in vitro of haemoglobin present in blood samples from insulin-depe ndent diabetic and non-diabetic human subjects and from spontaneously diabetic, insulin-dependent BB/Edinburgh (BB/E) rats. The percentage g lycated haemoglobin after incubation (37 degrees C, 5 h) with delta-GL (25 mmol/l) was significantly (P<0.002) higher than that observed usi ng an equimolar concentration of glucose. Intravenous administration o f delta-GL (1 g/kg) to non-diabetic BB/E rats also significantly incre ased glycation of haemoglobin (6.0+/-0.1% vs 4.9+/-0.1%, P<0.01) where as intravenous injection of an identical dose of glucose had no signif icant effect (5.1+/-0.1% vs 5.0+/-0.2%). These results support the hyp othesis that nonenzymatic glycation of proteins involves attachment by both native and oxidised monosaccharides. Further investigation of th e interactions between diabetes-associated increases in oxidative stre ss and glycation on the development and progression of the vascular co mplications of diabetes is necessary. (C) 1997 Elsevier Science B.V.