1994 Fiscal Year Final Research Report Summary
cDNA and Genomic Cloning of Human Insulin-sensitive Phosphodiesterase.
| Project/Area Number |
05670840
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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 Chiba University, School of Medicine Second Department of Internal Medicine Lecturer, 医学部, 講師 (50009578)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Glucokinae gene / Mutation / Type 2 (non-sinsulin-dependent) diabetes mellitus / PCR / SSCP / Insulin secretion |
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| Research Abstract |
Mutations were screened for in the glucokinse gene of 25 Japanese patients with Type 2 (non-insulin-dependent) diabetes mellitus using PCR-SSCP.A variant pattern was detected in exon 5 of one patient.Direct sequencing of this exon revealed a single mucleotide substitution in codon 188 (GCT-ACT) of one of two alleles resulting in the mutation of Ala-188-Thr, an invariant residue in the sequence of all mammalian glucokinases and hexokinases. This mutation was not found in 40 normal control subjects. The proband had been diagnosed with Type 2 diabetes at the ageof 62 years.
Four other members of her family have the same mutation and all have Type 2 diabetes or impaired glucose tolerane. The yougest age at diagnosis of Type 2 diabetes in these other members was 13 years, suggesting that her pedigree was maturity-onset diabetes of the young (MODY). All subjects with the Thr-188 mutation show a decreased insulin secretory response during oral glucose tolerance testing. Mutation in the glucokinase gene associated with Type 2 diabetes have been previously identified in Caucasian (French and British) subjects. This study indicates that mutations in this gene are also implicated in the development of Type 2 diabetes in Asians. Further studies are required to determine the frequency of mutations in glucokinase among Japanses patients with Type 2 diabetes.
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