Pleiotropic effect of pyridoxamine on diabetic complications via CD36 expression in KK-Ay/Ta mice

Published:January 14, 2009DOI:https://doi.org/10.1016/j.diabres.2008.11.008

      Abstract

      Aim

      Pyridoxamine inhibits the development of diabetic complications. CD36 is a receptor/transporter which binds fatty acids of lipoproteins. The objective of the present study was to examine the pleiotropic effects of pyridoxamine, especially CD36 expression in KK-Ay/Ta mice with type 2 diabetic nephropathy.

      Methods

      KK-Ay/Ta mice were divided into 2 groups as follows: pyridoxamine treatment group and a tap water group as controls. The urinary ACR, fasting serum insulin, TG and lipoprotein subclasses were measured as biochemical parameters. The renal expressions of malondialdehyde (MDA) were evaluated by immunohistochemistry. CD36 mRNA expressions in kidney and adipose tissue were also evaluated using real-time PCR.

      Results

      Pyridoxamine decreased levels of urinary ACR, serum TG, especially VLDL and fasting serum insulin. MDA accumulation in the pyridoxamine treated group was significantly lower than those in the non-treatment group. The CD36 accumulation and mRNA expressions in kidney and adipose tissue in the treatment group were significantly higher than those in the non-treatment group.

      Conclusions

      It appears that pyridoxamine ameliorated lipid peroxidation and insulin resistance in KK-Ay/Ta mice. This pleiotropic effect of pyridoxamine was related to CD36 expression in the kidney and adipose tissue.

      Keywords

      To read this article in full you will need to make a payment

      References

        • Brownlee M.
        • Vlassara H.
        • Kooney A.
        • Ulrich P.
        • Cerami A.
        Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking.
        Science. 1986; 232: 1629-1632
        • Singh R.
        • Barden A.
        • Mori T.
        • Beilin L.
        Advanced glycation end-products: a review.
        Diabetologia. 2001; 44: 129-146
        • Khalifah R.G.
        • Baynes J.W.
        • Hudson B.G.
        Amadorins: novel post-Amadori inhibitors of advanced glycation reactions.
        Biochem. Biophys. Res. Commun. 1999; 257: 251-258
        • Degenhardt T.P.
        • Alderson N.L.
        • Arrington D.D.
        • Beattie R.J.
        • Basgen J.M.
        • Steffes M.W.
        • et al.
        Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat.
        Kidney Int. 2002; 61: 939-950
        • Onorato J.M.
        • Jenkins A.J.
        • Thorpe S.R.
        • Baynes J.W.
        Pyridoxamine, an inhibitor of advanced glycation reactions, also inhibits advanced lipoxidation reactions. Mechanism of action of pyridoxamine.
        J. Biol. Chem. 2000; 275: 21177-21184
        • Jain S.K.
        • Lim G.
        Pyridoxine and pyridoxamine inhibits superoxide radicals and prevents lipid peroxidation, protein glycosylation, and (Na+ + K+)-ATPase activity reduction in high glucose-treated human erythrocytes.
        Free Radic. Biol. Med. 2001; 30: 232-237
        • Chetyrkin S.V.
        • Mathis M.E.
        • Ham A.J.
        • Hachey D.L.
        • Hudson B.G.
        • Voziyan P.A.
        Propagation of protein glycation damage involves modification of tryptophan residues via reactive oxygen species: inhibition by pyridoxamine.
        Free Radic. Biol. Med. 2008; 44: 1276-1285
        • Horiuchi S.
        • Sakamoto Y.
        • Sakai M.
        Scavenger receptors for oxidized and glycated proteins.
        Amino Acids. 2003; 25: 283-292
        • Endemann G.
        • Stanton L.W.
        • Madden K.S.
        • Bryant C.M.
        • White R.T.
        • Protter A.A.
        CD36 is a receptor for oxidized low density lipoprotein.
        J. Biol. Chem. 1993; 268: 11811-11816
        • Abumrad N.
        • Harmon C.
        • Ibrahimi A.
        Membrane transport of long-chain fatty acids: evidence for a facilitated process.
        J. Lipid Res. 1998; 39: 2309-2318
        • Abumrad N.A.
        • el-Maghrabi M.R.
        • Amri E.Z.
        • Lopez E.
        • Grimaldi P.A.
        Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36.
        J. Biol. Chem. 1993; 268: 17665-17668
        • Furuhashi M.
        • Ura N.
        • Nakata T.
        • Shimamoto K.
        Insulin sensitivity and lipid metabolism in human CD36 deficiency.
        Diabetes Care. 2003; 26: 471-474
        • Kuniyasu A.
        • Ohgami N.
        • Hayashi S.
        • Miyazaki A.
        • Horiuchi S.
        • Nakayama H.
        CD36-mediated endocytic uptake of advanced glycation end products (AGE) in mouse 3T3-L1 and human subcutaneous adipocytes.
        FEBS Lett. 2003; 537: 85-90
        • Ito T.
        • Tanimoto M.
        • Yamada K.
        • Kaneko S.
        • Matsumoto M.
        • Obayashi K.
        • et al.
        Glomerular changes in the KK-Ay/Ta mouse: a possible model for human type 2 diabetic nephropathy.
        Nephrology (Carlton). 2006; 11: 29-35
        • Usui S.
        • Hara Y.
        • Hosaki S.
        • Okazaki M.
        A new on-line dual enzymatic method for simultaneous quantification of cholesterol and triglycerides in lipoproteins by HPLC.
        J. Lipid Res. 2002; 43: 805-814
        • Takatori A.
        • Ishii Y.
        • Itagaki S.
        • Kyuwa S.
        • Yoshikawa Y.
        Amelioration of the beta-cell dysfunction in diabetic APA hamsters by antioxidants and AGE inhibitor treatments.
        Diabetes Metab. Res. Rev. 2004; 20: 211-218
        • Coburn C.T.
        • Knapp Jr., F.F.
        • Febbraio M.
        • Beets A.L.
        • Silverstein R.L.
        • Abumrad N.A.
        Defective uptake and utilization of long chain fatty acids in muscle and adipose tissues of CD36 knockout mice.
        J. Biol. Chem. 2000; 275: 32523-32529
        • Pravenec M.
        • Landa V.
        • Zidek V.
        • Musilova A.
        • Kren V.
        • Kazdova L.
        • et al.
        Transgenic rescue of defective Cd36 ameliorates insulin resistance in spontaneously hypertensive rats.
        Nat. Genet. 2001; 27: 156-158
        • Lewis G.F.
        • Carpentier A.
        • Adeli K.
        • Giacca A.
        Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes.
        Endocr. Rev. 2002; 23: 201-229
        • Susztak K.
        • Bottinger E.
        • Novetsky A.
        • Liang D.
        • Zhu Y.
        • Ciccone E.
        • et al.
        Molecular profiling of diabetic mouse kidney reveals novel genes linked to glomerular disease.
        Diabetes. 2004; 53: 784-794
        • Chen Z.
        • Ishibashi S.
        • Perrey S.
        • Osuga J.i.
        • Gotoda T.
        • Kitamine T.
        • et al.
        Troglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice: pleiotropic effects on CD36 expression and HDL.
        Arterioscler. Thromb. Vasc. Biol. 2001; 21: 372-377
        • Tanimoto M.
        • Gohda T.
        • Kaneko S.
        • Hagiwara S.
        • Murakoshi M.
        • Aoki T.
        • et al.
        Effect of pyridoxamine (K-163), an inhibitor of advanced glycation end products, on type 2 diabetic nephropathy in KK-A(y)/Ta mice.
        Metabolism. 2007; 56: 160-167