Pathophysiological Role of Amadori-Glycated Proteins in Diabetic Microangiopathy

Casper G. Schalkwijk; Mariska Lieuw-a-Fa; Victor W. M. van Hinsbergh; Coen D. A. Stehouwer

doi:10.1055/s-2002-32042

Seminars in Vascular Medicine, Table of Contents

Semin Vasc Med 2002; 2(2): 191-198
DOI: 10.1055/s-2002-32042

Pathophysiological Role of Amadori-Glycated Proteins in Diabetic Microangiopathy

Casper G. Schalkwijk^1, ⁴ , Mariska Lieuw-a-Fa^2, ⁴ , Victor W.M. van Hinsbergh^2, ^4, ⁵ , Coen D.A. Stehouwer^3, ⁴

¹Department of Clinical Chemistry, Vrije Universiteit Medical Center, Amsterdam
²Department of Physiology, Vrije Universiteit Medical Center, Amsterdam
³Department of Internal Medicine, Vrije Universiteit Medical Center, Amsterdam, the
⁴Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
⁵Gaubius Laboratory TNO-PG, Leiden, The Netherlands

Abstract

ABSTRACT

Early and advanced nonenzymatic glycation of proteins are increased in diabetes. Although Amadori-glycated proteins are the major glycated modifications, most studies so far have focused on the role of advanced glycation end-products (AGEs) in diabetes-related vascular complications. It was only recently that the role of Amadori-glycated proteins has come under consideration. Here we review data that point to an important role of Amadori-modified glycated serum proteins in diabetic microangiopathy. Amadori-glycated albumin induces the activation of glomerular mesangial and endothelial cells to a phenotype that may be linked to the pathogenesis of diabetic microangiopathy, that is, by the stimulation of protein kinase C, activation of transforming growth factor β, and the expression of extracellular matrix proteins. In type 1 diabetic patients, levels of Amadori-glycated proteins are independently associated with nephropathy and retinopathy. Reduction of Amadori-glycated albumin levels in diabetic animal models ameliorates the progression of nephropathy and retinopathy, indicating a causal role of Amadori-glycated proteins in the pathogenesis of diabetic nephropathy and retinopathy. Based on these data, inhibition of Amadori-glycated albumin may be a target for reduction of diabetic vascular complications.

KEYWORDS

Diabetes - Amadori-glycated albumin - glycation - AGEs - endothelial function - nephropathy - retinopathy

Full Text

References

REFERENCES

1 Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med . 1993; 329 977-986
2 United Kingdom Prospective Diabetes Study Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet . 1998; 352 837-853
3 Ruderman N B, Williamson J R, Brownlee M. Glucose and diabetic vascular disease. FASEB J . 1992; 6 2905-2914
4 Vlassara H, Bucala R, Striker L. Biology of disease. Pathogenic effects of advanced glycosylation: biochemical, biologic and clinical implications for diabetes and aging. Lab Invest . 1994; 70 138-151
5 Curtiss L K, Witztum J L. A novel method for generating region-specific monoclonal antibodies to modified proteins. J Clin Invest . 1983; 72 1427-1438
6 Makita Z, Vlassara H, Cerami A, Bucala R. Immunochemical detection of advanced glycosylation end products in vivo. J Biol Chem . 1992; 267 5133-5138
7 Iberg N, Fluckiger R. Nonenzymatic glycosylation of human serum albumin in vitro. J Biol Chem . 1983; 258 6142-6146
8 Thornalley P J, Langborg A, Minhas H S. Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose. Biochem J . 1999; 344 109-116
9 Edelstein D, Brownlee M. Mechanistic studies of advanced glycation end product inhibition by aminoguanidine. Diabetes . 1992; 41 26-29
10 Schalkwijk C G, Ligtvoet N, Twaalfhoven H. Amadori-albumin in type I diabetic patients: correlation with markers of endothelial function, association with diabetic nephropathy and localization in retinal capillaries. Diabetes . 1999; 48 2446-2453
11 Chen H JC, Cerami A. Mechanisms of inhibition of advanced glycosylation by aminoguanidine in vitro. J Carbohydrate Chem . 1993; 12 731-742
12 Soulis Liparoto T, Cooper M, Papazoglou D. Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rat. Diabetes . 1991; 40 1328-1334
13 Hammes H, Martin S, Federlin K. Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy. Proc Natl Acad Sci USA . 1991; 88 11555-11558
14 Cameron N E, Cotter M A, Dines K. Effects of aminoguanidine on peripheral nerve function and polyol pathway metabolites in streptozotocin-diabetic rats. Diabetologia . 1992; 35 946-950
15 Dolhofer R, Wieland O H. Increased glycosylation of serum albumin in diabetes mellitus. Diabetes . 1980; 29 417-422
16 Dyer D G, Dunn J A, Thorpe S R. Accumulation of Maillard reaction products in skin collagen in diabetes and aging. J Clin Invest . 1993; 91 2463-2469
17 Stehouwer C DA, Lambert J, Donker A JM. Endothelial dysfunction and pathogenesis of diabetic angiopathy. Cardiovasc Res . 1997; 34 55-68
18 Cohen M P, Clements R S, Cohan J A. Glycated albumin promotes a generalized vasculopathy in the db/db mouse. Biochem Biophys Res Comm . 1996; 218 72-75
19 Cohen M P, Hud E. Production and characterization of monoclonal antibodies against human glycoalbumin. J Immunol Methods . 1989; 117 121-129
20 McCance D R, Dyer D G, Dunn J A. Maillard reaction products and their relation to complications in insulin-dependent diabetes mellitus. J Clin Invest . 1993; 91 2470-2478
21 Sakai H, Jinde K, Suzuki D. Localization of glycated proteins in the glomeruli of patients with diabetic nephropathy. Nephrol Dial Transplant . 1996; 66-71
22 Ghiggeri G M, Candiano G, Delfino G. Glycosyl albumin and diabetic microalbuminuria: demonstration of an altered renal handling. Kidney Int . 1984; 25 565-570
23 Layton G J, Jerums G. Effect of glycation of albumin on its renal clearance in normal and diabetic rats. Kidney Int . 1988; 33 673-676
24 Londoño I, Bendayan M. Temporary effects of circulating Amadori products on glomerular filtration properties in the normal mouse. Am J Physiol Renal Physiol . 2001; 280 F103-F111
25 Jensen P K, Christiansen J S, Steven K. Renal function in streptozotocin-diabetic rats. Diabetologia . 1981; 21 409-414
26 Sabbatini M, Sansone G, Uccello F. Early glycosylation products induce glomerular hyperfiltration in normal rats. Kidney Int . 1992; 42 875-881
27 McVerry B A, Fisher C, Hopp A. Production of pseudodiabetic renal glomerular changes in mice after repeated injections of glucosylated proteins. Lancet . 1980; 1 738-740
28 Ghigger G M, Candiano G, Delfino G. Glycosyl albumin and diabetic microalbuminuria: demonstration of an altered renal handling. Kidney Int . 1984; 25 565-570
29 Cohen M P, Hud E, Wu V-Y. Amelioration of diabetic nephropathy by treatment with monoclonal antibodies against glycated albumin. Kidney Int . 1994; 45 1673-1679
30 Cohen M P, Ziyadeh F N. Role of Amadori-modified nonenzymatically glycated serum proteins in the pathogenesis of diabetic nephropathy. J Am Soc Nephrol . 1996; 7 183-190
31 Cohen M P, Masson N, Hud E. Inhibiting albumin glycation ameliorates diabetic nephropathy in the db/db mouse. Exp Nephrol . 2000; 8 135-143
32 Clements R S, Robison W G, Cohen M P. Anti-glycated albumin therapy ameliorates early retinal microvascular pathology in db/db mice. J Diab Comp . 1998; 12 28-33
33 Predescu D, Simionescu M, Simionescu N. Binding and transcytosis of glycoalbumin by the microvascular endothelium of the myocardium: evidence that glycoalbumin behaves as a bifunctional ligand. J Cell Biol . 1988; 107 1729-1738
34 Wu V-Y, Cohen M P. Identification of aortic endothelial cell binding proteins for Amadori adducts in glycated albumin. Biochem Biophys Res Commun . 1993; 193 1131-1136
35 Wu V-Y, Shearman C W, Cohen M P. Identification of calnexin as a binding protein for Amadori-modified glycated albumin. Biochem Biophys Res Commun . 2001; 284 602-606
36 Wu V-Y, Cohen M P. Receptors specific for Amadori-modified glycated albumin on murine endothelial cells. Biochem Biophys Res Commun . 1994; 198 734-739
37 Wu V-Y, Cohen M P. Evidence for a ligand receptor system mediating the biologic effects of glycated albumin in glomerular mesangial cells. Biochem Biophys Res Commun . 1995; 15 207:521-528
38 Salazar R, Brandt R, Krantz S. Expression of fructosyllysine receptors on human monocytes and monocyte-like cell lines. Biochim Biophys Acta . 1995; 1266 57-63
39 Krantz S, Salazar R, Brandt R. Purification and partial amino acid sequencing of a fructosyllysine-specific binding protein from cell membranes of the monocyte-like cell line U937. Biochim Biophys Acta . 1995; 1266 109-112
40 Salazar R, Brandt R, Kellermann J. Purification and characterization of a 200 kDa fructosyllysine-specific binding protein from cell membranes of U937 cells. Glycoconj J . 2000; 17 713-716
41 Brandt R, Landmesser C, Vogt L. Differential expression of fructosyllysine-specific receptors on monocytes and macrophages and possible pathophysiological significance. Diabetologia . 1996; 39 1140-1147
42 Schmidt A M, Vianna M, Gerlach M. Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface. J Biol Chem . 1992; 267 14987-14997
43 Araki N, Higashi T, Mori T. Macrophage scavenger receptor mediates the endocytic uptake and degradation of advanced glycation end-products of the Maillard reaction. Eur J Biochem . 1995; 230 408-415
44 Cohen M P, Hud E, Wu V-Y. Glycated albumin modified by Amadori adducts modulates aortic endothelial cell biology. Moll Cell Biochem . 1995; 143 73-79
45 Amore A, Cirina P, Mitola S. Nonenzymatically glycated albumin (Amadori adducts) enhances nitric oxide synthase activity and gene expression in endothelial cells. Kidney Int . 1997; 51 27-35
46 Chen S, Cohen M P, Lautenslager G T. Glycated albumin stimulates TGF-β production and protein kinase C activity in glomerular endothelial cells. Kidney Int . 2001; 59 673-681
47 Cohen M P, Wu V-Y, Cohen J A. Glycated albumin stimulates fibronectin and collagen IV production gene by glomerular endothelial cells. Biochem Biophys Res Commun . 1997; 238 91-94
48 Cohen M P, Ziyadeh F N. Amadori glucose adducts modulate mesangial cell growth and collagen gene expression. Kidney Int . 1994; 45 475-484
49 Ziyadeh F N, Han D-C, Cohen J A. Glycated albumin stimulates fibronectin gene expression in glomerular mesangial cells: involvement of the transforming growth factor-beta system. Kidney Int . 1998; 53 631-638
50 Cohen M P, Ziyadeh F N, Lautenslager G T. Glycated albumin stimulation of PKC-beta activity is linked to increased collagen IV in mesangial cells. Am J Physiol . 1999; 276 F684-F690
51 Cohen M P, Shea E, Shearman C W. ERK mediates effects of glycated albumin in mesangial cells. Biochem Biophys Res Commun . 2001; 283 641-643
52 Ichiki T, Funakoshi Y, Ito K. Expression of monocyte chemoattractant protein-1 by nonenzymatically glycated albumin (Amadori adducts) in vascular smooth muscle cells. Biochem Biophys Res Commun . 2000; 269 666-670
53 Hattori Y, Kakishita H, Akimoto K. Glycated serum albumin-induced vascular smooth muscle cell proliferation through activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway by protein kinase C. Biochem Biophys Res Commun . 2001; 281 891-896