| Budget Amount *help |
¥36,400,000 (Direct Cost: ¥36,400,000)
Fiscal Year 2004: ¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 2003: ¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 2002: ¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 2001: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Research Abstract |
Unlike Caucasian patients with type 2 diabetes showing insulin resistance mainly due to obesity, the defect of insulin secretion is the main cause of type 2 diabetes in Japan. In order to understand the tissue specificity of endocrine pancreas, it is important to clarify the expression profile of mRNAs in the pancreatic islets. Toward the identification of a complete set of genes expressed in human pancreatic islets, we have determined ESTs of 21,267 clones randomly selected from a cDNA library of human pancreatic islet tumors. Clustering analysis generated 6,157 non-redundant sequences comprising 2,323 groups and 3,834 singletons. The sequences also were compared with the EST databases including ESTs from normal pancreatic islet, insulinoma, and fetal pancreas. Since 3,384 genes were newly found to be expressed in human pancreatic islets and 587 of them were unique to the islets, we have considerably expanded the catalog of genes expressed in endocrine pancreas.
We have also established a first database of ESTs from rat pancreatic islet and R1Nm5F cells. Two cDNA libraries were constructed using mRNAs from rat pancreatic islet and RINm5F cells to cover a wider spectrum of expressed genes. 40,710 clones were randomly selected from the two libraries and partially sequenced. Clustering analysis and homology search using both 3'-and 5'-ESTs revealed 10,406 non-redundant transcripts representing 4,078 known genes or homologs and 6,328 unknown genes. Of the unknown sequences showing no match to dbEST from other sources, 779 were found to be encoded by exon-intron organization in the corresponding genomic sequences, suggesting that these are newly found as actually expressed. The larger collection of pancreatic islet-related ESTs should provide a better genome source for molecular studies of differentiation, tissue-specific functions, and tumorigenesis of endocrine pancreas as well as for genetic studies of diabetes mellitus, especially in Japanese.
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