Glyceraldehyde-derived advanced glycation end products (AGEs). A novel biomarker of postprandial hyperglycaemia in diabetic rats

Abstract

There is a growing body of evidence that postprandial hyperglycaemia plays an important role in accelerated atherosclerosis and may be a therapeutic target for preventing cardiovascular disease (CVD) in diabetes. However, there is no convenient biomarker that could reflect cumulative postprandial hyperglycaemia in diabetes. We have recently found that glyceraldehyde can rapidly react with amino groups of proteins to form glyceraldehyde-derived advanced glycation end products (AGEs), which evoke vascular inflammation and endothelial dysfunction, thereby being implicated in accelerated atherosclerosis in diabetes. In this study, we examined whether glyceraldehyde-derived AGEs were a biomarker that could reflect cumulative postprandial hyperglycaemia in Goto-Kakizaki (GK) rats fed twice a day. GK rats at 8 weeks of age were divided into 2 groups; either the vehicle (VEH) or 50 mg/kg of nateglinide (NAT) was administered twice daily just before each meal. After 6 weeks, nateglinide treatment was found to not only prevent postprandial hyperglycaemia, but also reduce glyceraldehyde-derived AGE levels in GK rats fed twice a day. However, there was no significant difference in HbA1c or glucose-derived AGE levels between the two groups. The present study demonstrated for the first time that glyceraldehyde-derived AGEs, but not HbA1c or glucose-derived AGEs, were a biomarker that could reflect cumulative postprandial hyperglycaemia in diabetic rats. Glyceraldehyde-derived AGEs may be a novel therapeutic target for preventing CVD in diabetes.

Theoretical studies on models of lysine-arginine cross-links derived from α-oxoaldehydes: a new mechanism for glucosepane formation

“…On the other hand, Ahmed et al classified AGEs to the first four in aforementioned ones [1,2]. Interestingly, clinical studies have shown that GlycerAGEs are more important than GLC-AGEs in cardiovascular disease (CVD) and nonalcoholic steatohepatitis (NASH) in diabetes [31,32].…”

An α-glucosidase inhibitor, acarbose treatment decreases serum levels of glyceraldehyde-derived advanced glycation end products (AGEs) in patients with type 2 diabetes

“…Further, recently, we found that serum levels of glyceraldehydederived AGEs rather than HbA 1c could reflect cumulative postprandial hyperglycemia in type 2 diabetic rats [7]. These observations led us to speculate that acarbose treatment reduced serum levels of glyceraldehyde-derived AGEs, which could contribute to its cardioprotective properties in vivo.…”

Suppression of antioxidant Nrf-2 and downstream pathway in H9c2 cells by advanced glycation end products (AGEs) via ERK phosphorylation

“…It has been suggested that glyceraldehyde-derived AGEs increase the risk of cardiovascular disease [39]. Our previous study demonstrated that glyceraldehyde-derived AGEs increase cell hypertrophy via ERK phosphorylation [40].…”