cDNA and Genomic Cloning of Human Insulin-sensitive Phosphodiesterase.

人胰岛素敏感磷酸二酯酶的 cDNA 和基因组克隆。

• 批准号: 05670840
• 负责人: MAKINO Hideichi
• 金额: $ 1.34万
• 依托单位: Chiba University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670840/
• 关键词: Glucokinae gene; Mutation; Type 2 (non-sinsulin-dependent) diabetes mellitus; PCR; SSCP; Insulin secretion; サイクリックAMP分解酵素; cDNAクローニング; 遺伝子クローニング; ヒト脂肪細胞; 糖尿病

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.

采用PCR-SSCP技术对25例日本2型（非胰岛素依赖型）糖尿病患者的葡萄糖激酶基因进行了突变筛选。在一名患者的外显子5中检测到一种变异模式。对该外显子的直接测序显示，导致Ala-188-Thr（所有哺乳动物葡萄糖激酶和己糖激酶序列中的不变残基）突变的两个等位基因之一的密码子188 （GCT-ACT）中的一个核苷酸替换。在40例正常对照中未发现该突变。先证者在62岁时被诊断出患有2型糖尿病。她家族的其他四名成员也有同样的突变，并且都患有2型糖尿病或糖耐量受损。在其他成员中，诊断为2型糖尿病的最小年龄为13岁，这表明她的血统是年轻人的成熟型糖尿病（MODY）。所有携带Thr-188突变的受试者在口服葡萄糖耐量试验中都表现出胰岛素分泌反应下降。与2型糖尿病相关的葡萄糖激酶基因突变先前已在白种人（法国和英国）受试者中发现。这项研究表明，该基因的突变也与亚洲人2型糖尿病的发展有关。需要进一步的研究来确定日本2型糖尿病患者中葡萄糖激酶突变的频率。

项目成果

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Shimada F.et al: "Type 2(non-insulin-dependent)diabetes mellitus associated with a mutation of the glucokinase gere in a Japanese family" Diabetologia. 36. 433-437 (1993)

Shimada F.等人：“日本家族中与葡萄糖激酶基雷突变相关的 2 型（非胰岛素依赖性）糖尿病”Diabetologia。

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