| Project/Area Number |
06671034
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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 |
内分泌・代謝学
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| Research Institution | Yamaguchi University |
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Principal Investigator |
MATSUTANI Akira Yamaguchi University School of Medicine, Third Department of Internal Medicine, Lccturer, 医学部・附属病院, 講師 (10190464)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | NIDDM / Glucokinase gene / Promoter / GLUT1 / GLUT2 |
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| Research Abstract |
We evaluated the promoter activity of islet GCK promoter variants and implicated its patho-physiological role in glucose metabolism. The promoter region containing polymorphic region at -30 (G to A) from the islet transcription initiation site, were PCR amplified from genomic DNA of 60 NIDDM patients and 56 non-diabetic subjects, whose genotypes were determined by SSCP and direct sequence. The frequency of the rare promoter with the sequence A at -30 was not different between NIDDM and the non-diabetic. The human islet promoter activity was assessed by transfecting HIT cells with the luciferase expression plasmid. The luciferase activity in the cells transfected with the promoter-luciferase plasmids containing the sequence A at -30 was significantly lower than that with the plasmids containing the sequence G.Oral glucose tolerance test (OGTT) was carried out in 22 non-diabetic subjects ; 8 subjects with G/G,10 with G/A,and 4 with A/A.Subjects with the sequence A showed higher plasma glucose levels on OGTT than subjects with the sequence G.Insulin levels were not significantly different among groups. All 8 subjects with G/G showed normal glucose tolerance, but 6 of 10 subjects with G/A and 3 of 4 subjects with A/A had impaired glucose tolerance. These data suggest that the promoter function is affected in the individual with the sequence A at -30, resulting in impaired glucose tolerance associated with GCK dysfunction. The present results thus suggest the possibility that a naturally occurring variant of the GCK promoter may contribute to the susceptibility to NIDDM in Japanese.
GLUT1, GLUT2 genes does not seem to have a major in the development of NIDDM.
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