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

B. M. Kim, S. Y. Kim, S. Lee, Y. J. Shin, Bon Hong Min, M. Bendayan, I. S. Park

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)311-320
Number of pages10
JournalDiabetologia
Volume49
Issue number2
DOIs
Publication statusPublished - 2006 Feb 1

Fingerprint

Clusterin
Pancreatic Ducts
Insulin-Secreting Cells
Insulin
Cell Differentiation
Pancreas
Keratin-20
Endocrine Cells
C-Peptide
Islets of Langerhans
Transfection
Intercellular Signaling Peptides and Proteins
Complementary DNA
Cell Culture Techniques
Epithelial Cells
Hormones
Gene Expression
Glucose

Keywords

  • Beta cells
  • Clusterin
  • Differentiation
  • Duct cells

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Kim, B. M., Kim, S. Y., Lee, S., Shin, Y. J., Min, B. H., Bendayan, M., & Park, I. S. (2006). Clusterin induces differentiation of pancreatic duct cells into insulin-secreting cells. Diabetologia, 49(2), 311-320. https://doi.org/10.1007/s00125-005-0106-2

Clusterin induces differentiation of pancreatic duct cells into insulin-secreting cells. / Kim, B. M.; Kim, S. Y.; Lee, S.; Shin, Y. J.; Min, Bon Hong; Bendayan, M.; Park, I. S.

In: Diabetologia, Vol. 49, No. 2, 01.02.2006, p. 311-320.

Research output: Contribution to journalArticle

Kim, BM, Kim, SY, Lee, S, Shin, YJ, Min, BH, Bendayan, M & Park, IS 2006, 'Clusterin induces differentiation of pancreatic duct cells into insulin-secreting cells', Diabetologia, vol. 49, no. 2, pp. 311-320. https://doi.org/10.1007/s00125-005-0106-2
Kim, B. M. ; Kim, S. Y. ; Lee, S. ; Shin, Y. J. ; Min, Bon Hong ; Bendayan, M. ; Park, I. S. / Clusterin induces differentiation of pancreatic duct cells into insulin-secreting cells. In: Diabetologia. 2006 ; Vol. 49, No. 2. pp. 311-320.
@article{5a0ee1b2c68f424ba82b53975dc49136,
title = "Clusterin induces differentiation of pancreatic duct cells into insulin-secreting cells",
abstract = "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.",
keywords = "Beta cells, Clusterin, Differentiation, Duct cells",
author = "Kim, {B. M.} and Kim, {S. Y.} and S. Lee and Shin, {Y. J.} and Min, {Bon Hong} and M. Bendayan and Park, {I. S.}",
year = "2006",
month = "2",
day = "1",
doi = "10.1007/s00125-005-0106-2",
language = "English",
volume = "49",
pages = "311--320",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - Clusterin induces differentiation of pancreatic duct cells into insulin-secreting cells

AU - Kim, B. M.

AU - Kim, S. Y.

AU - Lee, S.

AU - Shin, Y. J.

AU - Min, Bon Hong

AU - Bendayan, M.

AU - Park, I. S.

PY - 2006/2/1

Y1 - 2006/2/1

N2 - 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.

AB - 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.

KW - Beta cells

KW - Clusterin

KW - Differentiation

KW - Duct cells

UR - http://www.scopus.com/inward/record.url?scp=31844452407&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=31844452407&partnerID=8YFLogxK

U2 - 10.1007/s00125-005-0106-2

DO - 10.1007/s00125-005-0106-2

M3 - Article

VL - 49

SP - 311

EP - 320

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 2

ER -