Incomplete Re-Expression of Neuroendocrine Progenitor/Stem Cell Markers is a Key Feature of β-Cell Dedifferentiation
| Autor: | Fang-Xu Jiang, Grant Morahan, A. Neelankal John |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Programmed cell death Endocrinology Diabetes and Metabolism medicine.medical_treatment Nerve Tissue Proteins 030209 endocrinology & metabolism Stem cell marker Cell Line Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Endocrinology Insulin-Secreting Cells Internal medicine Insulin Secretion medicine Animals Insulin Transcription factor Cell Proliferation Progenitor Glucose Transporter Type 2 Homeodomain Proteins biology Endocrine and Autonomic Systems Stem Cells Cell Dedifferentiation Glucagon Glucose 030104 developmental biology Cell culture Trans-Activators biology.protein PDX1 GLUT2 Biomarkers Transcription Factors |
| Zdroj: | Journal of Neuroendocrinology. 29 |
| ISSN: | 0953-8194 |
| DOI: | 10.1111/jne.12450 |
| Popis: | There is increasing evidence to suggest that type 2 diabetes mellitus (T2D), a pandemic metabolic disease, may be caused by β-cell dedifferentiation (βCD). However, there is currently no universal definition of βCD, and the underlying mechanism is poorly understood. We hypothesise that a high-glucose in-vitro environment mimics hyperglycaemia in vivo and that β cells grown in this milieu over a long period will undergo dedifferentiation. Herein, we report that the pancreatic β cell line MIN6 grown under a high-glucose condition did not undergo massive cell death but exhibited a glucose-stimulated insulin-secreting profile similar to that of immature β cells. The expression of insulin and the glucose-sensing molecule glucose transporter 2 (Glut2) in late passage MIN6 cells was significantly lower than the early passage at both the RNA and protein levels. Mechanistically, these cells also expressed significantly less of the “pancreatic and duodenal homebox1” (Pdx1) β-cell transcription factor. Finally, passaged MIN6 cells dedifferentiated to demonstrate some features of β-cell precursors as well as neuroendocrine markers in addition to expressing both glucagon and insulin. Thus, we concluded that high-glucose passaged MIN6 cells provide a cellular model of β-cell dedifferentiation that can help researchers develop a better understanding of this process. These findings provide new insights that may enhance knowledge of the pathophysiology of T2D and facilitate the establishment of a novel strategy by which this disease can be treated. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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