Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells / 당뇨병
Korean Diabetes Journal
;
: 475-484, 2009.
Article
in Korean
| WPRIM
| ID: wpr-126157
ABSTRACT
BACKGROUND:
Despite a recent breakthough in human islet transplantation for treating type 1 diabetes mellitus, the limited availability of donor pancreases remains a major obstacle. Endocrine cells within the gut epithelium (enteroendocrine cells) and pancreatic beta cells share similar pathways of differentiation during embryonic development. In particular, K-cells that secrete glucose-dependent insulinotropic polypeptide (GIP) have been shown to express many of the key proteins found in beta cells. Therefore, we hypothesize that K-cells can be transdifferentiated into beta cells because both cells have remarkable similarities in their embryonic development and cellular phenotypes.METHODS:
K-cells were purified from heterogeneous STC-1 cells originating from an endocrine tumor of a mouse intestine. In addition, a K-cell subclone expressing stable Nkx6.1, called "Kn4-cells," was successfully obtained. In vitro differentiation of K-cells or Kn4-cells into beta cells was completed after exendin-4 treatment and serum deprivation. The expressions of insulin mRNA and protein were examined by RT-PCR and immunocytochemistry. The interacellular insulin content was also measured.RESULTS:
K-cells were found to express glucokinase and GIP as assessed by RT-PCR and Western blot analysis. RT-PCR showed that K-cells also expressed Pdx-1, NeuroD1/Beta2, and MafA, but not Nkx6.1. After exendin-4 treatment and serum deprivation, insulin mRNA and insulin or C-peptide were clearly detected in Kn4-cells. The intracellular insulin content was also increased significantly in these cells.CONCLUSION:
K-cells are an attractive potential source of insulin-producing cells for treatment of type 1 diabetes mellitus. However, more experiments are necessary to optimize a strategy for converting K-cells into beta cells.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pancreas
/
Peptides
/
Phenotype
/
Tissue Donors
/
Venoms
/
C-Peptide
/
RNA, Messenger
/
Immunohistochemistry
/
Proteins
/
Blotting, Western
Limits:
Animals
/
Female
/
Humans
/
Pregnancy
Language:
Korean
Journal:
Korean Diabetes Journal
Year:
2009
Type:
Article
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