Glycadia, Inc.

The nonenzymatic condensation of glucose with albumin results in the formation of albumin modified by Amadori glucose adducts, the principal form in which glycated albumin exists in vivo.

This review focuses on (a) the utility of measurement of Amadori-modified glycated albumin (AGA) as a biomarker in diabetes, where elevated levels attend the hyperglycemic state; (b) the role of AGA as a causal factor in the pathogenesis of complications of diabetes; (c) effects on transport properties; and (d) structural and functional consequences of the modification of albumin by Amadori glucose adducts. It does not discuss counterparts with respect to Advanced Glycation Endproducts (AGE), which may be found in other publications.

Nonenzymatic glycation of albumin, which is increased in diabetes, has clinical relevance and pathophysiologic importance, with ramifications for the management of this disease, the development of its complications, and the transport of endogenous and exogenous ligands.

Appreciation of the manifold consequences of AGA has afforded new avenues for assessing clinical management of diabetes, awareness of the impact of nonenzymatic glycation on albumin biology, insights into the pathogenesis of vascular complications of diabetes, and avenues of investigation of and intervention strategies for these complications. This article is part of a Special Issue on albumin. This article is part of a Special Issue entitled Serum Albumin.

Increased nonenzymatic glycation of apolipoprotein (apo) B-containing lipoproteins impairs uptake and metabolism by the high-affinity low-density lipoprotein receptor and is one of the postsecretory modifications contributory to accelerated atherosclerosis in diabetes. The present study evaluated in vitro and in vivo effects of 2,2-chlorophenylaminophenylacetate to probe the influence of glycated lipoprotein on cholesterol homeostasis. This compound prevented the increased formation of glycated products in low-density lipoprotein incubated with 200 mmol/L glucose and the increased cholesteryl ester synthesis in THP-1 macrophages induced by apo B-containing lipoproteins preincubated with high glucose concentration. The elevated circulating concentrations of glycated lipoprotein and cholesterol and higher vascular levels of lipid peroxidation products observed in streptozotocin diabetic rats compared with nondiabetic controls were significantly reduced in diabetic animals treated for 6 months with test compound. These results are the first to demonstrate that inhibiting nonenzymatic glycation of apo B-containing lipoproteins ameliorates abnormalities contributory to hypercholesterolemia and atherogenic risk in diabetes.

Imbalanced generation of the Aβ42 peptide from the amyloid β protein precursor (APP) is implicated in the pathogenesis of Alzheimer's disease.The present study is the first to evaluate the ability of 2‐[3‐chlorophenylamino]phenylacetic acid (GLY‐230), a new drug in clinical development for the treatment of vascular complications of diabetes, to modulate Aβ42 levels in transgenic mice expressing APP.Oral administration of 7.5 mg/kg GLY‐230 twice a day for 14 days to APPswe transgenic mice aged 3 months significantly reduced brain Aβ42 and increased plasma Aβ42 levels by 50 and 20%, respectively.GLY‐230 readily entered the brain after administration of a dose (7.5 mg/kg) that decreased brain Aβ42.These results are the first to demonstrate that GLY‐230, which exhibits antiglycation but no cyclo‐oxygenase inhibitory properties, lowers brain Aβ42 levels in this experimental model of Alzheimer's disease.