Advanced glycation end products and diabetic nephropathy: a comparative study using diabetic and normal rats with methylglyoxal-induced glycation.
Hyperglycemia-related advanced glycation end product (AGE) formation is a key mechanism in diabetic nephropathy. Since methylglyoxal (MG) is a potent AGE precursor, we aimed to assess the role of MG-related AGE formation in the progression of renal damages. A comparative study between Wistar (W, normal) and Goto-Kakizaki (GK, nonobese type 2 diabetic) rats was performed at 6 and 14 months old and after 14 weeks of MG administration to 6-month-old rats. Diabetic rats showed progressive structural, biochemical, and functional alterations, including AGE, albuminuria, and tissue hypoxia, which were partially mimicked by MG administration to young GK rats. Aged Wistar rats had an impairment of some parameters, whereas MG administration caused a phenotype similar to young GK rats, including oxidative stress, impaired apoptotic and angiogenic markers, and structural lesions. MG accumulation specifically impaired several of the renal disease markers progressively observed in diabetic rats, and thus, it contributes to the progression of diabetic nephropathy.
Laboratory of Physiology-IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Lisa
L
Rodrigues
Paulo
P
Matafome
Joana
J
Crisóstomo
Daniela
D
Santos-Silva
Cristina
C
Sena
Paulo
P
Pereira
Raquel
R
Seiça
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009929:Organ Size; D011765:Pyruvaldehyde; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D015430:Weight Gain
D051017:Apoptosis Regulatory Proteins; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000804:Angiotensin II; D011765:Pyruvaldehyde