| Co-Investigator(Kenkyū-buntansha) |
KAWAMORI Ryuzo Juntendo University School of Medicine, Internal Medicine, Professor, 医学部, 教授 (00116021)
YAMAMOTO Shozo University of Tokushima, Biochemistry, Professor, 医学部, 教授 (50025607)
ARISAKA Tomoyuki Juntendo University School of Medicine, Internal Medicine, Research associator, 医学部, 助手 (30266043)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
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| Research Abstract |
Part 1(the first year) : Platelet arachidonate 12-lipoxygenase (12-LOX) activity and content in diabetic patients and normal subjects (N=26) were investigted.
[Subjects] Sixty three patients with NIDDM and 26 normal subjects were studied.
[Method]The activity of 12-LOX was assayd by incubation of [1-^<14>C] arachidonic acid with the platelets cytosol.The reaction mixture was extracted and separated by thin layr chromatography, and the radioactive end products were detected.
[Results] The enzyme activity over the protein concentration of platelet and spectific enzyme activity over the enzyme content of platelet in 12 cases of NIDDM without angiopathy, were significantly lower than the value of gender, BMI,and age-matched normal subjects(enzyme activity : P<0.006, specific enzyme activity : P<0.0007, respectively). Nevertheless, the enzyme content in DM cases, was not different from the value of normal subjects. A significant correlation was noted between the 12-LOX activity and both 1,5-an
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hydroglucitol and HbA_<1C>(r=0.369, r=-0.354 respectively). A slight correlation was also seen between the 12-LOX activity and fructosamine (r=-0.29, P<0.05)
Part 2(the second year) : Mesurements of urinary albumin and HbA_<1C> were determined in the NIDDM patients with and without decrease of 12-LOX activity in platelets to evaluate the association between persistent proteinuria and 12-LOX activity in platelts, and to clarify the correlation ship between microalbuminuria and HbA_<1C> values.
[subjects] Fifty eight NIDDN patients were divided into two groups by values of in platelets {the normal group : 12-LOX activity (ng/10min/5X10^7PLT) >1.1(N=18), the decrease group : 12-LOX activity<1.09(N=40}.
[Method] The presence of proteinuria was based on a single urine collection. Urinary albumin concentration was measured with a radical immunodiffusion technique. HbA_<1C> was evaluated by the column chromatographic method.
[Results]1) A significant correlation of HbA_<1C> values with urinary albumin excretions was observed in the decrease group(r=0.547, P<0.002). Nevertheless, correlation of HbA_<1C> values with urinary albumin excretions wasnot observed in the normal group. 2) Concentrations of urinary albumin excretion were increased in the decrease group(N=13) than that in the sex gender, age, duration-matched normal group(N=13)(P<0.04).
[Conclusion] These observations have implied that the platelet 12-LOX activity is inactivated in diabetic subjects with long standing hyperglycemia, and that decrease of 12-LOX activity in platelets may be a risk factor for diabetic nephropathy. Less
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