Effects of pyridoxamine (K-163) on glucose intolerance and obesity in high-fat diet C57BL/6J mice.
Advanced glycation end products (AGEs) contribute to the pathogenesis of diabetes-associated complications. Previously, we reported the possible effect of pyridoxamine (K-163), an AGE inhibitor, on improvement of glucose intolerance in type 2 diabetes mellitus KK-A(y)/Ta mice. Recently, AGEs and oxidative stress have been shown to induce insulin resistance. The objective of the present study is to examine the effect of pyridoxamine on glucose intolerance and oxidative stress. C57BL/6J mice were divided into 3 groups as follows: low-fat diet, high-fat diet, and high-fat diet with pyridoxamine treatment. Body and adipose tissue weight, serum insulin, hydrogen peroxide, malondialdehyde and AGE, and urinary 8-hydroxy-2'-deoxyguanosine levels were measured. Nicotinamide adenine dinucleotide phosphate subunits, antioxidant enzymes, and adipocytokine messenger RNA expressions in the adipose tissues were evaluated. Akt/protein kinase B activity and glucose transporter 4 translocation in skeletal muscle were also evaluated. Body and adipose tissue weights of the pyridoxamine treatment group were significantly decreased compared with those of the high-fat diet group. Pyridoxamine attenuated serum hydrogen peroxide, malondialdehyde and AGE, and urinary 8-hydroxy-2'-deoxyguanosine and nicotinamide adenine dinucleotide phosphate oxidase expression; increased antioxidant enzyme expression; and improved dysregulation of adipocytokines in adipose tissues. Pyridoxamine improved blood glucose levels after glucose injection and fasting hyperinsulinemia. Suppressed Akt/protein kinase B activity and glucose transporter 4 translocation in skeletal muscle in high-fat diet mice were improved by pyridoxamine treatment. It appears that the antioxidative effect of pyridoxamine is associated with improvement of glucose intolerance and obesity in C57BL/6J mice fed a high-fat diet. We assume that pyridoxamine may be useful in the treatment of the obesity-associated metabolic syndrome.
Hagiwara
Shinji
S
Department of Internal Medicine, Division of Nephrology, Juntendo University School of Medicine, Tokyo, Japan.
Gohda
Tomohito
T
Tanimoto
Mitsuo
M
Ito
Takamichi
T
Murakoshi
Maki
M
Ohara
Ikko
I
Yamazaki
Takahiko
T
Matsumoto
Masakazu
M
Horikoshi
Satoshi
S
Funabiki
Kazuhiko
K
Tomino
Yasuhiko
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D054392:Adipokines / Q000737:chemistry / Q000235:genetics; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000652:urine; D017127:Glycation End Products, Advanced / Q000097:blood; D006861:Hydrogen Peroxide / Q000097:blood; D007150:Immunohistochemistry; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D019255:NADPH Oxidases / Q000737:chemistry / Q000235:genetics; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000652:urine; D011733:Pyridoxamine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000097:blood; D014280:Triglycerides / Q000097:blood
D054392:Adipokines; D000975:Antioxidants; D004041:Dietary Fats; D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D014280:Triglycerides; D008315:Malondialdehyde; D011733:Pyridoxamine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002784:Cholesterol; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D003849:Deoxyguanosine