- Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells.
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Esder Lee, Jun Mo Yu, Min Kyung Lee, Gyeong Ryul Ryu, Seung Hyun Ko, Yu Bae Ahn, Sung Dae Moon, Ki Ho Song
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Korean Diabetes J. 2009;33(6):475-484. Published online December 1, 2009
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DOI: https://doi.org/10.4093/kdj.2009.33.6.475
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- 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.
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Citations
Citations to this article as recorded by  - Reprogramming of enteroendocrine K cells to pancreatic β-cells through the combined expression of Nkx6.1 and Neurogenin3, and reaggregation in suspension culture
Esder Lee, Gyeong Ryul Ryu, Sung-Dae Moon, Seung-Hyun Ko, Yu-Bae Ahn, Ki-Ho Song
Biochemical and Biophysical Research Communications.2014; 443(3): 1021. CrossRef
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