|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1999 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1998 : ¥2,300,000 (Direct Cost : ¥2,300,000)
To investigate pathogenesis of type 2 diabetes mellitus, we carried out to identify gene, by which type 2 diabetes mellitus with autosomal dominant inheritance was caused. First, we used Akita mouse which was known to be diabetic model mouse with autosomal dominant inheritance. Coworker (Koizumi) identified origin of abnormal gene in Akita mouse to be insulin gene. However, it was thought that human type 2 diabetes mellitus with autosomal dominant inheritance was not induced by this abnormality of insulin gene. To examine the other possible gene, we carried out subtraction of gene in isolated islets of starved rats from gene in normal isolated islets. The same method was also carried out using Akita Mouse. As candidate gene after subtraction method, the following genes were obtained ; RGS10, Thyroid receptor, GA binding protein, Death association protein, Hypothetical protein, C-ternminal binding protein. Motor protein, TSC2, mSlo, Aldehyde reductase, Cortactin, Chip, KIAA 0788 KIAA 1014, EST201725, EST203522, EST226122, EST238072, EST207832, EST220962. It was confirmed by Data base that only a gene(TSC2) among various genes mentioned above were demonstrated in the pancreatic tissue until now. It is well known that isolated islet contained four kinds of cells including insulin containing B-cell, glucagon containing A-cells. Somatostatin containing D-cell and pancreatic polypeptide containing pp- cell. Therefore, it seems necessary to confirm that various genes mentioned above are localized in the pancreatic B-cells. To answer this question, in situ hybridization method was carried out in formalin fixed rat pancreatic tissue using insulin gene as control. Although in situ hybridization of a few kinds of genes mentioned above was finished, these genes was not confirmed to be present in the pancreatic B cells. We continued to investigate in situ hybridization for remains of candidate genes.