title: Modulation of the cellular expression of circulating advanced glycation end-product receptors in type 2 diabetic nephropathy.
abstract: BACKGROUND
  Advanced glycation end-products (AGEs) and their receptors are prominent contributors to diabetic kidney disease.
  
  
  METHODS
  Flow cytometry was used to measure the predictive capacity for kidney impairment of the AGE receptors RAGE, AGE-R1, and AGE-R3 on peripheral blood mononuclear cells (PBMCs) in experimental models of type 2 diabetes (T2DM) fed varied AGE containing diets and in obese type 2 diabetic and control human subjects.
  
  
  RESULTS
  Diets high in AGE content fed to diabetic mice decreased cell surface RAGE on PBMCs and in type 2 diabetic patients with renal impairment (RI). All diabetic mice had elevated Albumin excretion rates (AERs), and high AGE fed dbdb mice had declining Glomerular filtration rate (GFR). Cell surface AGE-R1 expression was also decreased by high AGE diets and with diabetes in dbdb mice and in humans with RI. PBMC expression of AGE R3 was decreased in diabetic dbdb mice or with a low AGE diet.
  
  
  CONCLUSIONS
  The most predictive PBMC profile for renal disease associated with T2DM was an increase in the cell surface expression of AGE-R1, in the context of a decrease in membranous RAGE expression in humans, which warrants further investigation as a biomarker for progressive DN in larger patient cohorts.
authors.affiliation: Glycation and Diabetes, Diabetes Division, Baker IDI Heart and Diabetes Institute, Melbourne 3004, Australia. karly.sourris@bakeridi.edu.au
authors.forename: Karly C
authors.initials: KC
authors.lastname: Sourris
authors.forename: Brooke E
authors.initials: BE
authors.lastname: Harcourt
authors.forename: Sally A
authors.initials: SA
authors.lastname: Penfold
authors.forename: Felicia Y T
authors.initials: FY
authors.lastname: Yap
authors.forename: Amy L
authors.initials: AL
authors.lastname: Morley
authors.forename: Philip E
authors.initials: PE
authors.lastname: Morgan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
authors.forename: Scott T
authors.initials: ST
authors.lastname: Baker
authors.forename: George
authors.initials: G
authors.lastname: Jerums
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Forbes
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood*; D005434:Flow Cytometry; D017127:Glycation End Products, Advanced / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic