Soluble RAGE in type 2 diabetes: association with oxidative stress.
Advanced glycation end products (AGEs) contribute to diabetic vascular complications by engaging the AGE receptor (RAGE). A soluble RAGE form (sRAGE) acts as a decoy domain receptor, thus decreasing AGE cellular binding. A cross-sectional comparison of sRAGE, asymmetric dimethylarginine (ADMA) plasma levels (index of endothelial dysfunction), and urinary 8-iso-prostaglandin (PG)F(2alpha) (marker of oxidative stress) was performed between 86 diabetic patients and 43 controls. Plasma sRAGE levels were significantly lower and ADMA levels were significantly higher in diabetic patients as compared to controls (P<0.0001). HbA1c and urinary 8-iso-PGF(2alpha) were correlated inversely with sRAGE and directly with ADMA. On multivariate analysis HbA1c was independently related to sRAGE levels in diabetic patients. Twenty-four of 86 patients with newly diagnosed diabetes and 12 patients in poor metabolic control were reevaluated after treatment with a hypoglycemic agent or insulin, respectively. Improvement in metabolic control by oral agents or insulin resulted in a significant increase in sRAGE and decrease in ADMA levels (P<0.0001). Thus, poor glycemic control reduces sRAGE levels, in association with enhanced oxidative stress and endothelial dysfunction in diabetes. These abnormalities are susceptible to modulation by improvement in metabolic control.
Devangelio
Eleonora
E
Center of Excellence on Aging and Departments of Medicine and Drug Sciences, University of Chieti "G. D'Annunzio" Schools of Medicine and Pharmacy, 66013 Chieti, Italy.
Santilli
Francesca
F
Formoso
Gloria
G
Ferroni
Patrizia
P
Bucciarelli
Loredana
L
Michetti
Noemi
N
Clissa
Cristina
C
Ciabattoni
Giovanni
G
Consoli
Agostino
A
Davì
Giovanni
G
D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood / Q000187:drug effects; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000097:blood / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood* / Q000187:drug effects
D001120:Arginine; D015237:Dinoprost; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C517652:hemoglobin A1c protein, human; C075750:8-epi-prostaglandin F2alpha; C018524:N,N-dimethylarginine