TY - JOUR
T1 - Amadori-glycated albumin in diabetic nephropathy
T2 - Pathophysiologic connections
AU - Chen, S.
AU - Cohen, M. P.
AU - Ziyadeh, F. N.
N1 - Funding Information:
Supported in part by the National Institutes of Health (grants DK-54143, DK-44513, DK-45191, DK-54608, and training grant DK-07006). Dr S. Chen is supported by a fellowship grant from the Juvenile Diabetes Foundation International.
PY - 2000
Y1 - 2000
N2 - Nonenzymatic glycation of proteins represents a major mechanism by which hyperglycemia leads to diabetic renal disease. Recent research has shown that Amadori-modified albumin, the principal glycated protein in plasma, elicits pathobiologic effects in cultured renal cells that are identical to those of high ambient glucose. When added to the incubation media of glomerular mesangial and endothelial cells, glycated albumin stimulates protein kinase C (PKC) activity, increases transforming growth factor-β (TGF-β) bioactivity, and induces gene overexpression and enhanced production of extracellular matrix proteins. These cellular events, whereby PKC-mediated TGF-β activation leads to increased matrix expression, are inextricably linked, and they form the central tenets of a pathophysiologic connection between glycated proteins and diabetic nephropathy. In vivo studies further corroborate the role of glycated proteins in the pathogenesis of diabetic nephropathy. Reduction or neutralization of glycated albumin in the db/db mouse model of type 2 diabetes significantly ameliorates the proteinuria, renal insufficiency, mesangial expansion, and overexpression of matrix proteins. In human type 1 diabetes, the plasma-glycated albumin concentration is independently associated with the presence of nephropathy. Abrogating the biologic effects of increased glycated albumin has novel therapeutic potential in the management of renal complications in diabetes.
AB - Nonenzymatic glycation of proteins represents a major mechanism by which hyperglycemia leads to diabetic renal disease. Recent research has shown that Amadori-modified albumin, the principal glycated protein in plasma, elicits pathobiologic effects in cultured renal cells that are identical to those of high ambient glucose. When added to the incubation media of glomerular mesangial and endothelial cells, glycated albumin stimulates protein kinase C (PKC) activity, increases transforming growth factor-β (TGF-β) bioactivity, and induces gene overexpression and enhanced production of extracellular matrix proteins. These cellular events, whereby PKC-mediated TGF-β activation leads to increased matrix expression, are inextricably linked, and they form the central tenets of a pathophysiologic connection between glycated proteins and diabetic nephropathy. In vivo studies further corroborate the role of glycated proteins in the pathogenesis of diabetic nephropathy. Reduction or neutralization of glycated albumin in the db/db mouse model of type 2 diabetes significantly ameliorates the proteinuria, renal insufficiency, mesangial expansion, and overexpression of matrix proteins. In human type 1 diabetes, the plasma-glycated albumin concentration is independently associated with the presence of nephropathy. Abrogating the biologic effects of increased glycated albumin has novel therapeutic potential in the management of renal complications in diabetes.
KW - Glomerulopathy
KW - Hyperglycemia
KW - Nonenzymatic glycation
KW - Protein kinase C
KW - Transforming growth factor-β
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U2 - 10.1046/j.1523-1755.2000.07707.x
DO - 10.1046/j.1523-1755.2000.07707.x
M3 - Review article
C2 - 10997689
AN - SCOPUS:2142749214
SN - 0098-6577
VL - 58
SP - S40-S44
JO - Kidney International, Supplement
JF - Kidney International, Supplement
IS - 77
ER -