title: Evidence of O-linked N-acetylglucosamine in diabetic nephropathy.
abstract: OBJECTIVE
  There is increasing evidence that O-linked N-acetylglucosamine (O-GlcNAc) plays an important role in cell signaling pathways. It has also been reported that increases in O-GlcNAc contribute to the development of diabetes and diabetic complications; however, little is known about O-GlcNAc levels in diabetic nephropathy (DNP). Therefore the goal of this study was to determine whether O-GlcNAc could be detected in human kidney biopsy specimens, and if so to examine whether O-GlcNAc levels were increased in the kidneys of patients with DNP compared to the non-diabetic individuals.
  
  
  METHODS
  Kidney biopsy specimens were obtained from type-2 diabetic patients (n=6) and patients diagnosed with thin basement membrane nephropathy (n=7) were used as non-diabetic controls. O-GlcNAc levels were assessed by immunohistochemistry using the anti-O-GlcNAc antibody CTD110.6.
  
  
  RESULTS
  We show that O-GlcNAc modification of proteins can be detected in the human kidney biopsy specimens. Furthermore, in diabetic patients, we found significantly increased numbers of O-GlcNAc positive cells in the glomeruli and significantly elevated staining in the tubuli (both in the nucleus and in the cytosol). In addition we also observed an intense, granular O-GlcNAc staining specifically in diabetic tubuli.
  
  
  CONCLUSIONS
  In light of the increase in O-GlcNAc staining in the diabetic patients, we propose that increased O-GlcNAc levels might contribute to the development of diabetic nephropathy.
authors.affiliation: 2nd Department of Medicine and Nephrological Center, University of Pécs, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Degrell
authors.forename: Judit
authors.initials: J
authors.lastname: Cseh
authors.forename: Márton
authors.initials: M
authors.lastname: Mohás
authors.forename: Gergo A
authors.initials: GA
authors.lastname: Molnár
authors.forename: László
authors.initials: L
authors.lastname: Pajor
authors.forename: John C
authors.initials: JC
authors.lastname: Chatham
authors.forename: Norbert
authors.initials: N
authors.lastname: Fülöp
authors.forename: István
authors.initials: I
authors.lastname: Wittmann
mesh_terms: D000117:Acetylglucosamine / Q000096:biosynthesis*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D006984:Hypertrophy; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis*
chemical_list: D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D000117:Acetylglucosamine