2000 Fiscal Year Final Research Report Summary
Adrenal androgens as new drugs for insulin resistance
| Project/Area Number |
11671093
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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 |
Endocrinology
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| Research Institution | Yokohama City University |
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Principal Investigator |
SEKIHARA Hisahiko Yokohama City University School of Medicine, Professor, 医学部, 教授 (80126094)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Tatsuya Yokohama City University School of Medicine, Associate Professor, 医学部, 助教授 (90205659)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Adrenal androgen / DHEA / G6Pase / Diabetir (db / db) mice / G6Pase gene Promoter |
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| Research Abstract |
Dehydroepiandrosterone (DHEA) is reported to improve hyperglycemia and insulin resistance in deabetic C57BL/KsJ-db/db mice. Our previous studies showed that the activity and mRNA levels of the hepatic gluconeogenic enzyme glucose-6-phosphatase (G6Pase) was increased in diabetic db/db mice despite hyperinsulinemia compared to the control, i.e., non-diabetic db/+m mice. DHEA,similarly to troglitazone, decreased the activity and mRNA expression of G6Pase in db/db mice. Therefore, DHEA is considered to improve hyperglycemia and insulin resistance by decreasing the activity and mRNA levels of hepatic G6Pase. To elucidate further the mechanism of DHEA on the G6Pase gene, we evaluated the reporter-gene luciferase activities. Approximately 3.9 Kbp G6Pase promoter+pGL3 basic vector was kindly provided by Dr.Schmoll and H4 II E hepatoma cells were transfected with this construct. After transfection, dexamethazone (1μM), and DHEA (1μM) were each and in combination added to the medium and the luciferase activity was measured. The results showed that dexamethazone increased the luciferase activity. DHEA exhibited decreased activity in the presence of dexamethazone. These data suggest that DHEA decreases the G6Pase gene promoter activity by inhibiting the glucocorticoid action in H4IIE cells.
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