The effect of delta-gluconolactone, an oxidised analogue of glucose, on the nonenzymatic glycation of human and rat haemoglobin.
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 glycation. This pathway involves monosaccharide autoxidation to a reactive 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 a potent glycating agent in vitro of haemoglobin present in blood samples from insulin-dependent diabetic and non-diabetic human subjects and from spontaneously diabetic, insulin-dependent BB/Edinburgh (BB/E) rats. The percentage glycated haemoglobin after incubation (37 degrees C, 5 h) with delta-GL (25 mmol/l) was significantly (P < 0.002) higher than that observed using an equimolar concentration of glucose. Intravenous administration of delta-GL (1 g/kg) to non-diabetic BB/E rats also significantly increased glycation of haemoglobin (6.0 +/- 0.1% vs 4.9 +/- 0.1%, P < 0.01) whereas intravenous injection of an identical dose of glucose had no significant effect (5.1 +/- 0.1% vs 5.0 +/- 0.2%). These results support the hypothesis that nonenzymatic glycation of proteins involves attachment by both native and oxidised monosaccharides. Further investigation of the interactions between diabetes-associated increases in oxidative stress and glycation on the development and progression of the vascular complications of diabetes is necessary.
Lindsay
R M
RM
Department of Medicine, University of Edinburgh, Western General Hospital, UK.
Smith
W
W
Lee
W K
WK
Dominiczak
M H
MH
Baird
J D
JD
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D003925:Diabetic Angiopathies / Q000097:blood / Q000209:etiology; D005942:Gluconates / Q000494:pharmacology*; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism*; D006031:Glycosylation; D006454:Hemoglobins / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D007783:Lactones; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D011913:Rats, Inbred BB
D005942:Gluconates; D006442:Glycated Hemoglobin; D006454:Hemoglobins; D007783:Lactones; C010730:beta-glucono-1,5-lactone