Effect of AOB, a fermented-grain food supplement, on oxidative stress in type 2 diabetic rats.
Reactive oxygen species (ROS) play an important role in the pathogenesis of diabetic complications. Antioxidant Biofactor (AOB) is a mixture of commercially available fermented grain foods and has strong antioxidant activity. This study investigated the effect of AOB supplementation of standard rat food on markers of oxidative stress and inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with type 2 diabetes. Blood glucose, hemoglobin A1c, plasma free fatty acid, triacylglycerol and plasminogen activator inhibitor-1 (PAI-1) were significantly higher in OLETF rats than in non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats at 29 weeks. AOB (6.5% of diet) was given to rats during 29-33 weeks of diabetic phase in OLETF rats. OLETF rats with AOB supplementation showed decreased blood glucose, hemoglobin A1c, triacyglycerol, low density lipoprotein, cholesterol and PAI-1. Mitochondrial ROS production was significantly increased in heart, aorta, liver and renal artery of OLETF rats. Uncoupling protein 2 (UCP2) is known to regulate ROS production. We found aortic UCP2 protein expression increased in OLETF rats, and AOB returned UCP2 expression to normal. Aortic endothelial NO synthase (eNOS) was also increased in OLETF rats more than in LETO rats at 33 weeks. In contrast, phosphorylated vasodilator-stimulated phosphoprotein, an index of the NO-cGMP pathway, was significantly diminished. AOB increased eNOS proteins in LETO and OLETF rats. In conclusion, AOB significantly improved the NO-cGMP pathway via normalizing ROS generation in OLETF rats. The data suggest that dietary supplementation with AOB contributes to nutritional strategies for the prevention and treatment of type 2 diabetes mellitus.
Minamiyama
Yukiko
Y
Department of Anti-Aging Food Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho, Okayama, Japan. yukiko-m@md.okayama-u.ac.jp
Takemura
Shigekazu
S
Tsukioka
Takuma
T
Shinkawa
Hiroji
H
Kobayashi
Fumiko
F
Nishikawa
Yuriko
Y
Kodai
Shintaro
S
Mizuguchi
Shinjiro
S
Suehiro
Shigefumi
S
Okada
Shigeru
S
D000818:Animals; D001011:Aorta / Q000737:chemistry; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000517:prevention & control; D051275:Glucose Transporter Type 4 / Q000032:analysis; D006442:Glycated Hemoglobin / Q000032:analysis; D007473:Ion Channels / Q000032:analysis; D007501:Iron / Q000032:analysis; D015227:Lipid Peroxidation; D008055:Lipids / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D024101:Mitochondrial Proteins / Q000032:analysis; D052250:Nitric Oxide Synthase Type III / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000008:administration & dosage*; D010936:Plant Extracts / Q000008:administration & dosage*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D051381:Rats; D020334:Rats, Inbred OLETF; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071246:Uncoupling Protein 2
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D051275:Glucose Transporter Type 4; D006442:Glycated Hemoglobin; D007473:Ion Channels; D007501:Iron; D008055:Lipids; D024101:Mitochondrial Proteins; D052250:Nitric Oxide Synthase Type III; D010636:Phenols; D010936:Plant Extracts; D017395:Plasminogen Activator Inhibitor 1; D017382:Reactive Oxygen Species; D000071246:Uncoupling Protein 2; C495694:Slc2a4 protein, rat; C000604391:Ucp2 protein, rat; C501911:antioxidant biofactor AOB