Clusterin induces differentiation of pancreatic duct cells into insulin-secreting cells.
OBJECTIVE
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
These results suggest that clusterin can be considered as a potential morphogenic factor that promotes differentiation of pancreatic beta cells.
Kim
B M
BM
Department of Anatomy, College of Medicine, Inha University Incheon, Choong-Gu, Shinheung-Dong, Incheon 400-103, Korea.
Kim
S Y
SY
Lee
S
S
Shin
Y J
YJ
Min
B H
BH
Bendayan
M
M
Park
I S
IS
D000818:Animals; D002096:C-Peptide / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D051152:Clusterin / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D008297:Male; D010183:Pancreatic Ducts / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D046509:Tissue Culture Techniques; D014162:Transfection
D002096:C-Peptide; D051152:Clusterin; D018076:DNA, Complementary; D007328:Insulin; D012333:RNA, Messenger; D005947:Glucose