Pleiotropic effect of pyridoxamine on diabetic complications via CD36 expression in KK-Ay/Ta mice.
OBJECTIVE
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-A(y)/Ta mice with type 2 diabetic nephropathy.


METHODS
KK-A(y)/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-A(y)/Ta mice. This pleiotropic effect of pyridoxamine was related to CD36 expression in the kidney and adipose tissue.
Murakoshi
Maki
M
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Tanimoto
Mitsuo
M
Gohda
Tomohito
T
Hagiwara
Shinji
S
Ohara
Ikko
I
Toyoda
Hitoe
H
Ishikawa
Yuji
Y
Horikoshi
Satoshi
S
Tomino
Yasuhiko
Y
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D048909:Diabetes Complications / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007333:Insulin Resistance / Q000235:genetics; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011733:Pyridoxamine / Q000494:pharmacology* / Q000627:therapeutic use
D018955:CD36 Antigens; D007004:Hypoglycemic Agents; D008315:Malondialdehyde; D011733:Pyridoxamine