Modulation of CD36 protein expression by AGEs and insulin in aortic VSMCs from diabetic and non-diabetic rats.
OBJECTIVE
In type 2 diabetes, the interplay between cells and inflammatory mediators up-regulates CD36 expression in macrophages. The aim of this work was to investigate advanced glycation end products (AGE)-induced CD36 expression and its regulation by insulin in aortic vascular smooth muscle cells (VSMCs) from Goto-Kakisaki (GK) rats, a non-obese insulin model of both insulin resistance and type 2 diabetes. The context of overexpression of CD36 in aortas was also evaluated.


RESULTS
VSMCs were isolated and cultured from the aortas of GK rats and non-diabetic rats. The expression of proteins was evaluated by Western blot. The aortic production of superoxide anion (O(2)(.-)) was measured by luminescence on isolated tissue. AGEs and advanced oxidation protein products (AOPPs) were determined in plasma by fluorescence spectroscopy and spectrophotometry, respectively. AGE receptor (RAGE), NF-kappaB, and CD36 protein expression as well as O(2)(.-) production were higher in GK aortas than in control aortas, and AGEs and AOPPs were higher in GK plasma. In VSMCs from non-diabetic rats, insulin was able to reduce (10 nM) or suppress (100 nM) the protein overexpression of CD36 induced by AGEs-BSA. In contrast, in VSMCs from GK rats, insulin was unable to reduce AGEs-BSA-induced CD36 overexpression.


CONCLUSIONS
The results suggest an overexpression of CD36 in VSMCs from GK rats and impaired control by insulin. In the context of increased plasma AGEs, aortic RAGE overexpression and increased oxidative stress markers, the data are compatible with an AGEs induced CD36 overexpression in diabetes.
de Oliveira Silva
Cristina
C
Laboratoire de Nutrition Humaine et Athérogénèse (LNHA), EA 2993, Institut Universitaire de Recherche Clinique, Université Montpellier I, 641 Avenue du Doyen Giraud, 34093 Montpellier, France. cos@montp.inserm.fr
Delbosc
Sandrine
S
Araïs
Caroline
C
Monnier
Louis
L
Cristol
Jean-Paul
JP
Pares-Herbute
Nuria
N
D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation
D018955:CD36 Antigens; C008132:Cd36 protein, rat; D017127:Glycation End Products, Advanced; D007328:Insulin; D016328:NF-kappa B; D011506:Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; C081628:advanced glycation end products-bovine serum albumin; D013481:Superoxides; D012710:Serum Albumin, Bovine