Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells.
10.4093/kdj.2009.33.6.475
- Author:
Esder LEE
1
;
Jun Mo YU
;
Min Kyung LEE
;
Gyeong Ryul RYU
;
Seung Hyun KO
;
Yu Bae AHN
;
Sung Dae MOON
;
Ki Ho SONG
Author Information
1. Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. kihos@catholic.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Differentiation;
Enteroendocrine cells;
K-cell;
Nkx6.1 protein;
Pancreatic beta-cell
- MeSH:
Animals;
Blotting, Western;
C-Peptide;
Diabetes Mellitus, Type 1;
Embryonic Development;
Endocrine Cells;
Enteroendocrine Cells;
Epithelium;
Female;
Glucokinase;
Humans;
Immunohistochemistry;
Insulin;
Insulin-Secreting Cells;
Intestines;
Islets of Langerhans Transplantation;
Mice;
Pancreas;
Peptides;
Phenotype;
Pregnancy;
Proteins;
RNA, Messenger;
Tissue Donors;
Venoms
- From:Korean Diabetes Journal
2009;33(6):475-484
- CountryRepublic of Korea
- Language:Korean
-
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.
