RGD Reference Report - Clusterin induces differentiation of pancreatic duct cells into insulin-secreting cells. - Rat Genome Database

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Clusterin induces differentiation of pancreatic duct cells into insulin-secreting cells.

Authors: Kim, BM  Kim, SY  Lee, S  Shin, YJ  Min, BH  Bendayan, M  Park, IS 
Citation: Kim BM, etal., Diabetologia. 2006 Feb;49(2):311-20. Epub 2006 Jan 13.
RGD ID: 1582421
Pubmed: (View Article at PubMed) PMID:16411126
DOI: Full-text: DOI:10.1007/s00125-005-0106-2

AIMS/HYPOTHESIS: We recently reported that expression of the gene encoding clusterin (Clu) is upregulated in the regenerating pancreas, particularly in tissues undergoing differentiation. This led us to propose that clusterin participates in the cytodifferentiation of pancreatic tissue, particularly the endocrine islet cells. The aim of this study was to investigate whether clusterin induces the differentiation of duct-lining cells into insulin-secreting cells. METHODS: We isolated ductal tissue from rat pancreas and cultured it to develop epithelial cell explants for transfection of the Clu cDNA as well as for treatment of clusterin protein. RESULTS: The number of newly differentiated insulin cells increased 6.9-fold upon Clu overexpression compared with controls. Ins1 mRNA and peptide levels were also increased. Furthermore, glucose-stimulated insulin secretion was observed in the differentiated insulin cells. These cells were immunoreactive for insulin and C-peptide, but negative for other islet hormones and for cytokeratin-20, which indicates a fully differentiated state. Insulin cell differentiation was also increased in a dose-dependent manner by treating duct cells in culture with clusterin, indicating a growth-factor-like action of clusterin in insulin cell differentiation. CONCLUSIONS/INTERPRETATION: These results suggest that clusterin can be considered as a potential morphogenic factor that promotes differentiation of pancreatic beta cells.


Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Clu  (clusterin)

Additional Information