Abstract
Pancreatic islet cells have plasticity, such as the abilities to dedifferentiate and transdifferentiate. Islet cell conversion to other characteristic cell is largely determined by transcription factors, but significance of expression patterns of these transcription factors in human islet cells remained unclear. Here, we present the NKX6.1-positive ratio of glucagon-positive cells (NKX6.1+/GCG+ ratio) and the ARX-negative ratio of glucagon-positive cells (ARX−/GCG+ ratio) in 34 patients who were not administered antidiabetic agents. Both of NKX6.1+/GCG+ ratio and ARX−/GCG+ ratio negatively associated with relative beta cell area. And these ratios did not have significant correlation with other parameters including age, body mass index, hemoglobin A1c, fasting plasma glucose level or relative alpha-cell area. Our data demonstrate that these expression ratios of transcription factors in glucagon-positive cells closely correlate with the reduction of beta-cell volume in human pancreas.
Highlights
Pancreatic islet cells have plasticity, such as the abilities to dedifferentiate and transdifferentiate
We recently identified beta cells that expressed ARX or that did not express PDX-1, and alpha cells that did not express ARX or that express PDX-1 widely ranging from normal glucose tolerance to diabetic glucose tolerance stages, using human pancreatic fresh tissue samples obtained by p ancreatectomy[16]
We revealed that the NKX6.1-positive ratio and ARX-negative ratio of alpha cells increased with a reduction of beta-cell volume in human pancreas
Summary
Pancreatic islet cells have plasticity, such as the abilities to dedifferentiate and transdifferentiate. When transdifferentiation occurs, the expression patterns of transcription factors change in islet cells. Extreme loss of beta cells in mouse induces the conversion of alpha cells to beta cells, in which beta-cell-specific transcription factors such as pancreatic duodenal homeobox factor-1 (Pdx-1) and NK homeobox 6.1 (Nkx6.1) are expressed in alpha c ells[13]. All these phenomena are observed under artificial conditions. A study using lineage tracing in mouse revealed that immature beta cells present at islet periphery are in an intermediate transdifferentiation stage between alpha and beta cells[14]. The factors that promote the changes of these expression patterns of transcription factors in physiological condition in humans have not been elucidated
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