インスリン感受性からみたインスリン非依存型糖尿病の成因に関する遺伝学的研究

从胰岛素敏感性角度进行非胰岛素依赖型糖尿病病因的遗传学研究

• 批准号: 10470234
• 负责人: IWAMOTO Yasuhiko
• 金额: $ 0.83万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470234/
• 关键词: type 2 diabetes mellitus; insulin resistance; insulin sensitizer; PC-1; PPAR-γ; affected sib-pair analysis; MODY; インスリン抵抗性改善薬; 罹患同胞対法; インスリン非依存型糖尿病; イスンリン抵抗性; インスリン抵抗性改善剤; TNF-α

1. Tyrvosine kinase inhibitor PC-1 and insulin resistance : The mean PC-1 activity of the cultured dermal fibroblasts from NIDDM patients was significantly higher than that of non-diabetic control subjects.2. Serum leptin level as an indicator to predict the clinical efficacy of troglitazone (TRO) in patients with NIDDM : We investigated the relationship between serum leptin levels and clinical efficacy of TRO in 45 NIDDM patients. Reduction in FPG after TRO treatment was correlated with serum leptin and HOMA-R (insulin resistance index) at baseline, suggesting that serum leptin level at baseline control could be an useful indicator to predict the clinical efficacy of TRO in NIDDM.3. Polymorphism of PPAR-γand insulin resistance : Polymorphism of PPAR-γgene (Pro 12 Ala) was not correlated with insulin resistance or the clinical efficacy of insulin sensitizer.4. A genome-wide screen for type 2 diabetes susceptibility genes has been carried out in 270 affected sibpairs of type 2 diabetes, and 6 loci have been identified.5. Clinical characteristics of juvenile-onset type2 diabetes and genetic background : We investigated the mutatins in the HNF-1β(MODY5) and A to G mutation at nucleotide 3243 of the mitochondrial (mt) DNA in 54 juvenile-onset diabetic patients who had started kidney diialysis under 50 years of age. Six patients had 3243 mutation of mt DNA, suggesting that the mutation has a greater effect on the progression of diabetic nephropathy.

1.酪氨酸激酶抑制剂PC-1与胰岛素抵抗：培养的NIDDM患者真皮成纤维细胞PC-1活性明显高于非糖尿病对照组。血清瘦素水平作为预测曲格列酮(Tro)临床疗效的指标：我们观察了45例NIDDM患者血清瘦素水平与tro临床疗效的关系。TRO治疗后空腹血糖下降与基线时血清瘦素和HOMA-R(胰岛素抵抗指数)相关，提示基线对照时血清瘦素水平可作为预测TRO治疗NIDDM临床疗效的有用指标。PPAR-γ基因多态性与胰岛素抵抗：PPAR-γ基因(Pro12Ala)多态性与胰岛素抵抗及胰岛素敏感性的临床疗效无关。在270对受影响的2型糖尿病同胞中进行了2型糖尿病易感基因的全基因组筛查，已经确定了6个基因座。青少年起病2型糖尿病的临床特点和遗传背景：我们调查了54例在50岁以下开始进行肾脏透析的青少年起病糖尿病患者的人类神经营养因子-1DNA(MODY5)突变和线粒体(Mt)β第3243位核苷酸A到G突变。6例患者存在线粒体DNA 3243突变，提示该突变对糖尿病肾病的进展有较大影响。

项目成果

Teno,Shinichi: "Increased activity of membrane glycoprotein PC-1 in the fibroblast from ruon-insulin-dependent diaberes mellitus patient with lnsulis resistance."Diabetes Res Clin Pract. 45. 25-30 (1999)

Teno，Shinichi：“具有胰岛素抵抗的 ruon 胰岛素依赖性糖尿病患者的成纤维细胞中膜糖蛋白 PC-1 的活性增加。”糖尿病研究临床实践。

Teno,Shinichi: "An increased membrane glycoprotein PC-1 in a Werner's syndrome patient with rare compound heterozygous mutations." 東京女子医大雑誌. 69・6(in press). (1999)

Teno, Shinichi：“具有罕见复合杂合突变的维尔纳综合征患者的膜糖蛋白 PC-1 增加。” 东京女子医科大学杂志 69・6（出版中）。

Teno S, Kanno H, Oga S, Kumakura S, Kanamuro R, Iwamoto Y: "Increased activity of membrane glycoprotein PC-1 in the fibroblasts from non-insulin-dependent diabetes mellitus patients with insulin resistance."Dibetes Res Clin Pract. 45. 25-30 (1999)

Teno S、Kanno H、Oga S、Kumakura S、Kanamuro R、Iwamoto Y：“具有胰岛素抵抗的非胰岛素依赖型糖尿病患者的成纤维细胞中膜糖蛋白 PC-1 的活性增加。”糖尿病研究临床实践。

Maruyama S, Yanagisawa K, Kanamuro R, Teno S, Iwamoto Y: "Serum leptin level as an indicator to predict the clinical efficacy of troglitazone in patients with NIDDM."Dibetes Res Clin Pract. (in press). (2000)

Maruyama S、Yanagisawa K、Kanamuro R、Teno S、Iwamoto Y：“血清瘦素水平作为预测 NIDDM 患者曲格列酮临床疗效的指标。”糖尿病研究临床实践。

Teno,Shinichi: "Increased activity of membrane glycoprotein PC-1 in the fibroblast from non-insulin-dependent diabetes mellipus patient with insulin resistance" Diabetes Res Clin Pract. in press. (1999)

Teno，Shinichi：“具有胰岛素抵抗的非胰岛素依赖型糖尿病患者成纤维细胞中膜糖蛋白 PC-1 的活性增加”糖尿病研究临床实践。