Processing Advanced Glycation End Product-Modified Albumin by the Renal Proximal Tubule and the Early Pathogenesis of Diabetic Nephropathy
AYLIN M. OZDEMIR,
ULRICH HOPFER,
PENNY ERHARD,
VINCENT M. MONNIER,
MIRIAM F. WEISS,
AYLIN M. OZDEMIR
Departments of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
Search for more papers by this authorULRICH HOPFER
Departments of Physiology, Case Western Reserve University, Cleveland, Ohio 44106, USA
Search for more papers by this authorPENNY ERHARD
Departments of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
Search for more papers by this authorVINCENT M. MONNIER
Departments of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
Departments of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
Search for more papers by this authorCorresponding Author
MIRIAM F. WEISS
Departments of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
Address for correspondence: Miriam F. Weiss, M.D., Division of Nephrology, Department of Medicine, University Hospitals of Cleveland, 11100 Euclid Ave., Cleveland, OH 44106-5048. Voice: 216-844-8272; fax: 216-368-0767. [email protected]Search for more papers by this authorAYLIN M. OZDEMIR,
ULRICH HOPFER,
PENNY ERHARD,
VINCENT M. MONNIER,
MIRIAM F. WEISS,
AYLIN M. OZDEMIR
Departments of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
Search for more papers by this authorULRICH HOPFER
Departments of Physiology, Case Western Reserve University, Cleveland, Ohio 44106, USA
Search for more papers by this authorPENNY ERHARD
Departments of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
Search for more papers by this authorVINCENT M. MONNIER
Departments of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
Departments of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
Search for more papers by this authorCorresponding Author
MIRIAM F. WEISS
Departments of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
Address for correspondence: Miriam F. Weiss, M.D., Division of Nephrology, Department of Medicine, University Hospitals of Cleveland, 11100 Euclid Ave., Cleveland, OH 44106-5048. Voice: 216-844-8272; fax: 216-368-0767. [email protected]Search for more papers by this authorAbstract
Abstract: 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.
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