cDNA and Genomic Cloning of Human Insulin-sensitive Phosphodiesterase.

应用聚合酶链式反应-单链构象多态性分析技术对25例日本2型糖尿病患者的葡萄糖激肽基因突变进行了检测，其中1例患者的第5外显子检测到突变模式，直接测序发现该外显子188密码子的单核苷酸替换(GCT-ACT)导致了ALA-188-Thr的突变，Ala-188-Thr是所有哺乳动物糖激酶酶和己糖激酶酶序列中的不变残基。在40名正常对照组中未发现该突变。先证者在62岁时被诊断出患有2型糖尿病。她的家族其他四名成员都有相同的突变，都患有2型糖尿病或糖耐量受损。在这些其他成员中，被诊断为2型糖尿病的最小年龄为13岁，这表明她的家系是青年成熟型糖尿病(MODY)。在口服葡萄糖耐量试验中，所有携带Thr-188突变的受试者都表现出胰岛素分泌反应降低。先前已经在高加索人(法国和英国)受试者中发现了与2型糖尿病相关的葡萄糖激酶基因突变。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。

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.