Biomedical subjects

T Nishigori

Publications and source records attributed to T Nishigori.

8 recordsLinked to original sources

PubMed2003

Expression profile of mRNAs from human pancreatic islet tumors.

In order to understand the tIssue specificity of the endocrine pancreas, it is important to clarify the expression profile of mRNAs in various states of the tIssue. A total of approximately 9000 non-redundant expressed genes from human pancreatic islets and insulinoma have so far been determined as expressed sequence tags (ESTs) and deposited in public databases. In the present study towards the identification of a complete set of genes expressed in human pancreatic islets, we have determined 3'-ESTs of 21267 clones randomly selected from a cDNA library of human pancreatic islet tumors. Clustering analysis generated 6157 non-redundant sequences comprising 2323 groups and 3834 singletons. Nucleotide and peptide database searches show that 3103 of them represent known human sequences or homologs of genes identified in other species and 58 are new members of structurally related families. The sequences were classified on the basis of the putative protein functions encoded, and were assigned to the respective chromosome by database analysis. The sequences were also compared with the EST databases (dbEST and EPConDB) including ESTs from normal pancreatic islet, insulinoma, and fetal pancreas. Since 3384 genes were newly found to be expressed in human pancreatic islets and 587 of them were unique to the islets, this study has considerably expanded the catalog of genes expressed in the endocrine pancreas. 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 the endocrine pancreas as well as for genetic studies of diabetes mellitus.

Cloning, Molecular↗

PubMed2001

Genetic variation in the hepatocyte nuclear factor (HNF)-3alpha gene does not contribute to maturity-onset diabetes of the young in Japanese.

Heterozygous mutations in the genes encoding transcription factors in the hepatocyte nuclear factor (HNF) cascade are associated with maturity-onset diabetes of the young (MODY), a monogenic form of diabetes mellitus. However, these genes are responsible for only approximately 20% of the cases of MODY in Japanese patients. Searching for a novel MODY gene in this population, we investigated a candidate for encoding the forkhead transcription factor HNF-3alpha, which also belongs to the HNF-transcription cascade. The human HNF-3alpha gene, which was assigned to the segment near microsatellites D14S75 and AFM200ZH4 on chromosome 14 by radiation hybrid mapping, spans approximately 5 kb and consists of two exons. Ninety-five Japanese subjects with MODY/early-onset non-ketotic diabetes were screened for mutations in this gene. Direct sequencing of the exons and flanking regions identified one missense mutation (Ala-83-Thr) in exon 2 and three nucleotide alterations in the non-coding regions. However, their frequencies were not significantly different between MODY and control subjects, indicating that mutations in the HNF-3alpha gene are not a major cause of MODY in Japanese patients.

DNA-Binding Proteins↗

PubMed1996

Proinsulin cleaved by furin is processed to chromatographically mature insulin by carboxypeptidases in nonneuroendocrine cells.

Proinsulin is converted to mature insulin by two reactions, cleavage by the prohormone convertases PC2 and PC3, and removal of basic residues by carboxypeptidase H. These reactions are performed in the secretory granules of pancreatic beta cells. When we replaced the processing sites of proinsulin with furin-cleavable sites, the three nonneuroendocrine cell lines Hep G2, CHO, and NIH/3T3 produced insulin with the same size as synthetic human insulin. Although the three cell lines expressed different quantities of carboxypeptidase H mRNA, the cytosol fractions of the cells exhibited similar levels of carboxypeptidase activity, suggesting that additional carboxypeptidases were active. The insulins resulting from the three cell lines were eluted as a single peak on a cation-exchange chromatography column, indicating that proinsulin can be maturated to insulin even in nonneuroendocrine cells.

3T3 Cells↗

PubMed1974