1992 Fiscal Year Final Research Report Summary
Molecular mechanism of transcriptional regulation by insulin
| Project/Area Number |
03670122
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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 |
General medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
NOGUCHI Tamio Osaka University Nutr. & Physiol. Chem Assoc. Pro, 医学部, 助教授 (70135721)
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| Project Period (FY) |
1991 – 1992
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| Keywords | L-type pyruvate kinase gene / Glucokinase gene / Insulin response element / Transgeninic mice |
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| Research Abstract |
We produced transgenic mice containing the 5'-flanking region of the L-type pyruvate kinase (LPK) gene from nucleotide -189 50 +37, which includes an enhancer unit and TATA box as functional elements, linked to the chloramphenicol acetyltransferase (CAT) gene. Transgene expression was stimulated by both dietary glucose and fructose in the liber. The fusion gene was also transfected into cultured hepatocytes and the cells were incubated with or without insulin. Insulin stimulated expression of the CAT gene in the presence of glucose, but not in the presence of pyruvate. Thus, we suggest that an enhancer unit of the LPK gene is insulin response unit.
2. HNF1 binds to L-III, which constitutes an enhancer unit of the LPK gene. Expression of HNF1 was not under dietary control.
3. Using CAT assay, we showed that the 5'-flanking region of the glucokinase up to -1100 contained the DNA region responsive to insulin.
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