Genes involved in insulin secretion and improvement of detection method for gene mutations in diabetic patients

为了研究tRNALeu （UUR）线粒体基因突变引起糖尿病的患病率和临床特征，我们筛选了440例糖尿病母亲为糖尿病患者的线粒体基因突变核苷酸对（np） 3250、3256、3260、3271和3291，以及高达3243的A到G转位。本研究采用32p标记的序列特异性寡核苷酸（SSO）为探针的斑点杂交方法。虽然没有发现在np 3250、3256、3260或3291位点突变的糖尿病患者，但发现1例在np 3271位点携带T到C转捩，7例在3243位点携带a到G转捩。3271突变患者为一名39岁男性，仅通过饮食治疗血糖控制良好，没有听力障碍，也没有线粒体肌病、脑病、乳酸酸中毒和卒中样发作（MELAS）的症状。综上所述，在糖尿病患者中，3271突变的患病率约为3243突变的14%，而tRNALeu （UUR）的其他突变在母体传播的糖尿病中更为罕见。我们还克隆了胰腺β细胞中参与葡萄糖诱导胰岛素分泌的基因hGIRK2和mGPDH，并分析了这些基因在日本糖尿病患者中的突变。

To investigate the prevalence and clinical characteristics of diabetes mellitus caused by mitochondrial gene mutations in the tRNALeu (UUR), we screened 440 diabetic patients with diabetic mothers for mitochondrial gene mutations at nucleotide pair (np) 3250,3256,3260,3271 and 3291 in addition to an A to G transition at up 3243. The dot-blot hybridization method using 32P-labeled sequence-specific oligonucleotides (SSO) as probes was employed in this study. While no diabetic patients having a point-mutation at np 3250,3256,3260 or 3291 were found, one carrying a T to C transition at np 3271 and seven carrying an A to G transition at 3243 were identified. The patient with the 3271 mutation, a 39-year-old male, had excellent glycemic control with diet therapy alone and had neither hearing impairment nor symptoms suggesting mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). In summary, among diabetic patients, the prevalence of the 3271 mutation was about 14% that of the 3243 mutation, while other mutations in the tRNALeu (UUR) are even more rare in maternally transmitted diabetes.We have also cloned the gene involved in glucose-induced insulin secretion from pancreatic beta cells, hGIRK2 and mGPDH,and analyzed the mutations of these genes in Japanese diabetic patients.