OXIDATIVE STRESS AND EXERCISE : ESTABLISHMENT OF EXERCISE THERAPY FOR HEALTH PROMOTION AND PREVENTION OF DIABETES

1.本文采用气相色谱/质谱法和酶联免疫吸附法分别从红细胞中提取羧甲基缬氨酸血红蛋白（CMV-Hb），建立了红细胞膜氧化胆固醇3,5,7-胆甾醇（3,5,7- c）的检测体系。我们发现这些新的标志物反映了几个月的氧化应激积累，并且在糖尿病患者中它们增加了。我们评估了先前报道的10个与氧化应激相关的SNP，发现NAD(P)H氧化酶p22phox C242T和ACE I/D基因型的组合与动脉粥样硬化相关。我们应该进一步研究发现新的与氧化应激相关的SNP与糖尿病或动脉粥样硬化的关系。我们用1H-MRS检查了细胞内脂质（IMCL）和肝内脂质（IHL），用腹部MRI检查了内脏脂肪体积（VF）。我们发现，在非糖尿病性肥胖患者和2型糖尿病患者体重降低之前，短期生活方式的改变可以降低IMCL、IHL和VF。我们评估了不增加3、5、7-C和CNV-Hb运动（150-170 kcal+每日生活）和能量限制（30 kcal/IBW kg）对非糖尿病肥胖受试者6-12个月的影响。IMCL、HL、VF和血脂均得到改善，肝脏和肌肉的胰岛素敏感性得到改善。我们应该制定个性化的最佳运动和饮食方案，并评估其效果，以供进一步研究。

1.New marker of oxidative stress accumulationWe established the assay systems of 3,5,7-cholestatriene (3,5,7-C), a kind of oxycholesterol in RBC membrane, by GC/MS and carboxymethyl-valine hemoglobin (CMV-Hb) extracted from RBC by ELISA. We revealed that these new markers reflected accumulation of oxidative stress for several months and they increased in diabetic patients.2.Association of oxidative stress-related gene polymorphism with diabetes and atherosclerosisWe evaluated previously reported ten SNP related to oxidative stress and found that the combination of NAD(P)H oxidase p22phox C242T and ACE I/D genotypes was associated with atherosclerosis. We should further investigate to find new SNP related to oxidative stress associating with diabetes or atherosclerosis.3.Fine assessment of body fat distributionWe investigated intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) by 1H-MRS and visceral fat volume (VF) by abdominal MRI. We found that IMCL, IHL, and VF could be reduced by short term life style modification before reduction of BW in non-diabetic obese subjects and type 2 diabetic patients.4.Intervention of life style modification on non-diabetic obese subjectsWe evaluated the effect of exercise not increasing 3,5,7-C and CNV-Hb (150-170 kcal+daily life) and energy restriction (30 kcal/IBW kg) on non-diabetic obese subjects for 6-12 months. IMCL, HL,VF, and serum lipid profile were ameliorated, and insulin sensitivity in liver and muscle were improved. We should make individualized program of optimal exercise and diet, and evaluate its effect for further study.