1992 Fiscal Year Final Research Report Summary
Molecular Genetical and Functional Analysis in Insulin Receptor Gene Mutation
| Project/Area Number |
03671131
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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 | Chiba University School of Medicine |
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Principal Investigator |
MAKINO Hideichi Second Department of Internal Medicine, Assistant Professor, 医学部, 講師 (50009578)
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| Project Period (FY) |
1991 – 1992
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| Keywords | insulin receptor / gene mutation / insulin resistance / type A insulin resistance / leprechaunism / tyrosine kinase / NIDDM / diabetes mellitus |
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| Research Abstract |
Non-insulin-dependent diabetes mellitus (NIDDM) shows mild to moderate insulin resistance, but severe insulin resistance has been reported in some genetic syndromes. In order to understand the mechanism of insulin resistance in NIDDM, it is useful to first analyze this mechanism in these syndromes. We have identified four mutations in insulin receptor gene and analyzed the development of diabetes in these cases. Type A Chiba had deletion mutation in exon 17-22, Type A Yamanashi showed deletion of exon 14 and Type A Hokkaido-2 had a point mutation substituting Val for Gly in the 1008th amino acids in respective one allele. Leprechaun/Asahi showed two base pair deletion in exon 15 in one allele and low mRNA mutation in the other allele. In the pedigree and clinical analysis, a single mutant allele in the tyrosine kinase domain, such as Type A Chiba and Type A Hokkaido-2 showed dominant expression of diabetes, but the one in the transmembrane domain, such as Type A Yamanashi did not. The mutation in both alleles, such as Lep/Asahi showed severe forms of insulin resistance, such as leprechaunism.
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