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Toshiyuki Takeuchi

Publications and source records attributed to Toshiyuki Takeuchi.

40 records · Page 3Linked to original sources
PubMed2002

Up-regulation of the expression of activins in the pancreatic duct by reduction of the beta-cell mass.

Activins expressed in progenitor cells of the pancreas regulate differentiation of endocrine cells during development. Neogenesis of beta-cells takes place in adult animals under some conditions, and beta-cells are thought to arise from precursors locating in the pancreatic duct. In the present study, we investigated whether or not activins are expressed in the duct where beta-cell neogenesis is initiated. mRNA for the beta(A)- and beta(B)-subunits was expressed in isolated mouse pancreatic ducts. Immunohistochemically, the beta(A)-subunit was detected in the pancreatic duct and colocalized with cytokeratin, a marker of ductal cells. The beta(A)-subunit was also expressed in nestin-positive cells in the duct. Likewise, the beta(B)-subunit was detected in the pancreatic duct. In addition, mRNA for the type II and type IIB activin receptors was expressed in the duct. Expression of mRNA for two activin subunits was markedly increased after streptozotocin injection. Similarly, the mRNA expression was up-regulated after partial pancreatectomy. These results indicate that activins are expressed in the pancreatic duct and are up-regulated shortly after the reduction of the beta-cell mass. Induction of activins in the duct may be a critical step in the initiation of beta-cell neogenesis.

Activin Receptors↗
PubMed2002

Involvement of Rab27b in the regulated secretion of pituitary hormones.

We recently identified a novel set of Rab and its effector, Rab27a/granuphilin, that possibly regulates the exocytosis of insulin-containing, dense core granules in pancreatic beta-cells. In the present study we characterized another isoform, Rab27b, to further investigate the function of the Rab27 subfamily. Among the tissues examined, Rab27b is most abundantly expressed in pituitary tissue, where Rab27a is preferentially expressed. It is also significantly expressed in brain and spleen, where Rab27a is minimally expressed. Rab27a and Rab27b are differentially expressed in pituitary cell types that secrete different peptide hormones. Rab27b associates with secretory granules and granuphilin in the pituitary endocrine cell line AtT20. Furthermore, overexpression of its inactive mutant, Rab27b N133I, significantly inhibits basal and forskolin-induced ACTH secretion in AtT20 cells. These findings indicate that Rab27b is involved in pituitary hormone secretion, which further supports the idea that members of the Rab27 subfamily regulate the exocytosis of dense core granules containing peptide hormones in endocrine cells.

Adenoviridae↗
PubMed2000

Proprotein-Processing Endoprotease Furin and its Substrate Parathyroid Hormone-Related Protein Are Coexpressed in Insulinoma Cells.

Parathyroid hormone-related protein (PTHrP) is frequently produced in pancreatic endocrine tumors. PTHrP is synthesized as the precursor pro-PTHrP and undergoes a series of posttranslational processing reactions, among which cleavage of a 12 amino acid sequence from its precursor is crucial for the biological activation of PTHrP. This cleavage is catalyzed by furin, a proprotein-processing endoprotease that cleaves the consensus sequence -Arg-X-(Lys/Arg)-Arg-X-. We previously reported that furin is highly expressed in rat pancreatic islets during the perinatal stage and that the expression of furin in pancreatic-cells induces faster cell growth. From this, we postulated that furin may be co-expressed with PTHrP in insulinomas. We immunostained insulin, PTHrP, and furin in 21 human pancreatic endocrine tumors: 10 insulinomas, 5 VIPomas, 4 gastrinomas, and 2 somatostatinomas. Of these 21 endocrine tumors, furin was positively stained in all 10 insulinomas. Likewise, PTHrP was detected in the same insulinomas. We found one VIPoma and one gastrinoma contained a few insulin-positive cells scatteringly, which were also positive for furin and PTHrP. But other non-insulinoma endocrine tumors did not display furin and PTHrP positivity. We conclude that furin and its substrate pro-PTHrP are co-expressed specifically in insulinomas.

Journal Article↗