1986 Fiscal Year Final Research Report Summary
Abnormal metabolism of arachidonic acid and vascular disorder
| Project/Area Number |
60571070
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo Medical and Dental University (1986)
Tokyo Metropolitan Institute of Gerontology (1985) |
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Principal Investigator |
MUROTA Sei-itsu Tokyo Medical and Dental University, Faculty of Dentistry, Professor, 歯学部, 教授 (50072989)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAO Junko Tokyo Metropolitan Institute of Gerontology, 内分泌科, 兼務研究員 (10150880)
MORITA Ikuo Tokyo Medical and Dental University, Faculty of Dentistry, Associate professor, 歯学部, 助教授 (60100129)
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| Project Period (FY) |
1985 – 1986
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| Keywords | Arachidonate cascade / Atherosclerosis / 12-HETE / Prostaglandin / EPA / PDGF |
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| Research Abstract |
In investigations on the role of insulin on migration of rat aortic smooth muscle cells, migration of the cells was measured by a midified Boyden cnamber technique with 12-L-hydroxy-5,8,10,14-dicosa-tetraenoic acid (12-HETE) as a chemoattractant. Insulin itself was not a chemoattractant for these cells, and insulin added just before the migration assay did not affect cell migration in the presence or absence of 12-HETE.
Cells pretreated with insulin in culture dishes for a long period, however, showed a significant increase in migration induced by 12-HETE, and the increase depended on the insulin concentration: concentrations of insulin of 50uIU/ml caused about twofold increase in cell migration. On the other hand, long-term incubation with various concentrations of insulin (0.15-1000uIU/ml) did not affect nonspecific cell migration in the absence of 12-HETE. The stimulatory effect of insulin on cell migration gradually increased with the duration of insulin treatment, reaching a plateau after 4 days. Thus, insulin stimulated 12-HETE-induced smooth muscle cell migration in a time-and dose-dependent manner.
When the extracellular D-glucose concentration in the Boyden chamber was increased from 100 to 300 mg/dl, the stimulatory effect of insulin on 12-HETE-induced cell migration was augmented. This modulation by D-glucose was not due to an increase in the osmotic pressure of the medium, since addition of mannitol to increase the osmotic pressure did'not enhance the effect of insulin on cell migration. The present results indicate that insulin in a physiologic or pathophysiologic range stimulates 12-HETE-induced smooth muscle cell migration in a manner dependent on the extracellular D-glucose concentration. These findings are relevant to the increased development of atherosclerosis in subjects with hyper-insulinemia and hyperglycemia, as is seen in obesity and diabetes mellitus.
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Research Products
(11 results)
