Increased NKX6.1 expression and decreased ARX expression in alpha cells accompany reduced beta-cell volume in human subjects

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.