| Project/Area Number |
13557225
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Laboratory medicine
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| Research Institution | HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
MAEKAWA Masato HAMAMATSU UNIVERSITY, Faculty of Medicine, Professor, 医学部, 教授 (20190291)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Akira Daiichi Pure Chemical Co. Ltd., Assistant Manager, 診断薬研, 主任
HORII Toshinobu HAMAMATSU UNIVERSITY, Faculty of Medicine, Assistant Professor, 医学部附属病院, 助手 (80283430)
KANNO Takashi HAMAMATSU UNIVERSITY, Faculty of Medicine, Vice-President, 医学部, 副学長 (70051406)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥9,900,000 (Direct Cost: ¥9,900,000)
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| Keywords | Oxidized LDL / Malondialdehyde / Atherosclerosis / Diabetes Mellitus / Insulin / Statin / Fibrate / Anti-oxidation / 小粒子LDL / 中性脂肪 / HDL / 高脂血症 |
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| Research Abstract |
1)Insulin treatment prevents LDL from accelerated oxidation in patients with diabetes.
In a study population, we compared the level of malondialdehyde-modified LDL (MDA-LDL) with the concentrations of lipid parameteis in serum and found a strong correlation between MDA-LDL and apolipoprotein B (apo B) concentrations. Their interrelations had a turning point at an apo B concentration of 1,150 mg/l. In diabetic patients, the ratio of MDA-LDL/apo B increased at apo B concentrations above 1,150 mg/l. This ratio represents the extent of modification of apo B by MDA. In the control subjects, this ratio remained stable. When we divided the patients into medication groups (statins and insulin), we found that the 1,150 mg/l threshold disappeared. At apo B concentrations above 1,150 mg/l, the ratio of MDA-LDL/apo B in the stalin group was as high as that in the non-drug group. In the insulin group, the means of MDA-LDL/apo B in all ranges of apo B levels decreased to an extent statistically indis
… More
tinguishable from those of the control group. In conclusion, insulin therapy represses LDL oxidation even at apo B concentrations>1,150 mg/l and should be noted for its anti-oxidation properties.
2)Influence of fibrate treatment on malondialdehyde-modified LDL concentration.
Drug therapy is considered essential to the clinical prevention of atherosclerotic lesions in patients with diabetes mellitus (DM). To confirm the effects of fibrate therapy, we determined low-density lipoprotein (LDL) size by gradient gel electrophoresis and malondialdehyde-modified LDL (MDA-LDL) concentrations by enzyme-linked immunosolvent assay (ELISA) and clarified the association between apolipoprotein B (apo B) and MDA-LDL during the fibrate therapy. Mean MDA-LDL concentrations were higher in healthy men than in healthy women. There were no significant differences in mean MDA-LDL concentrations between age groups for males or females. According to the regression equation (y=0.063x+10.9) obtained for apo B and MDA-LDL concentrations with fibrate treatment, the apo B concentration in those may need to be decreased to 1260 mg/l to restore the MDA-LDL concentration to the control concentration (65 +/-25 units/l). This slope of the apoB/MDA-LDL regression line was approximately half of that with nd-drug treatment (y=0.109x-10.8). In conclusion, fibrate therapy had an effect on reducing serum MDA-LDL concentration in diabetic patients. Less
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