Role of Insulin Signal Transduction on the Regulation of Senescence
| Project/Area Number |
11672170
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
KUROKAWA Tomonori Hiroshima University, Faculty of medicine, Associate Professor, 医学部, 助教授 (00124793)
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| Co-Investigator(Kenkyū-buntansha) |
HAZEKI Osamu Hiroshima University, Faculty of Medicine, Professor, 医学部, 教授 (80142751)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | aging / insulin signal transduction / senescence-accelerated prone mouse (SAMP8) / blood glucose level / energy consumption / glucose oxidation / ATP production / mitochondria / 老化促進モデルマウス / SAMP8 / PI3-キナーゼ / チロシンリン酸化タンパク質 |
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| Research Abstract |
The signal transduction for insulin between senescence-accelerated prone mouse 8 (SAMP8) and age-matched senescence-accelerated resistant mouse 1 (SAMR1) as a control was compared. But, no difference in insulin effect on the reduction of blood glucose level of the two strains at any ages was observed. Additionally, there were also no difference in insulinstimulated 2-deoxy-D-glucose uptake into the adipocytes from the two strains and the contents of the phosphotyrosine and insulin receptor.
On the other hand, we found that the blood glucose level of SAMP8 from 10 weeks of age on wards was markedly decreased by a short fasting compared with that of age-matched SAMR1. Furthermore, we showed that the fasting effect in SAMP8 was observed more rapidly than that in SAMR1. At 5 weeks of age, however, there was no difference in the blood glucose level after a short fasting between the two strains. To study the cause by which the blood glucose in SAMP8 from 10 weeks of age onwards after a short fasting was much consumed, [6-^<14>C] glucose oxidation in dissociated intact cells from whole brain of both strains was investigated. The production of ^<14>CO_2 in 10-20 weeks old SAMP8 was higher than that in age-matched SAMR1, while no difference between the two strains at 5 weeks of age was observed. On the contrary, the ATP contents in the brain of 5-20 weeks old SAMP8 were the same with those in age-matched SAMR1.
The results indicated that the efficiency of ATP production in SAMP8 from 10 weeks of age onwards was deteriorated compared with that in age-matched SAMR1 because the glucose oxidation in SAMP8 was higher than that in SAMR1. Our results also suggest that the consumption of the blood glucose of SAMP8 may be increased as a compensation of the inefficient production of ATP in mitochondria.
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Report
(3 results)
Research Products
(6 results)
