Processing advanced glycation end product-modified albumin by the renal proximal tubule and the early pathogenesis of diabetic nephropathy.
Diabetes is characterized by increased quantities of circulating proteins modified by advanced glycation end products (AGEs). Proteins filtered at the glomerulus and presented to the renal proximal tubule are likely to be highly modified by AGEs. The proximal tubule binds, takes up, and catabolizes AGE-modified albumin by pathways different from those of unmodified albumin. These differences were examined in polarized, electrically resistant proximal tubular cells grown in monolayer culture. In patients with type 1 diabetes, urinary excretion of a lysosomal enzyme predicted the development of nephropathy.
Ozdemir
Aylin M
AM
Division of Nephrology, Department of Medicine, University Hospitals of Cleveland, 11100 Euclid Ave., Cleveland, OH 44106-5048, USA.
Hopfer
Ulrich
U
Erhard
Penny
P
Monnier
Vincent M
VM
Weiss
Miriam F
MF
D000118:Acetylglucosaminidase / Q000652:urine; D000419:Albuminuria / Q000503:physiopathology; D002478:Cells, Cultured; D003470:Culture Media; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism
D003470:Culture Media; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; C039217:fluorescein isothiocyanate bovine serum albumin; D012710:Serum Albumin, Bovine; D000118:Acetylglucosaminidase; D016650:Fluorescein-5-isothiocyanate