Increased frequency of β cells with abnormal NKX6.1 expression in type 2 diabetes but not in subjects with higher risk for type 2 diabetes.

Tengli Liu, Peng Sun, Jiaqi Zou, Le Wang, Guanqiao Wang, Na Liu, Yaojuan Liu, Xuejie Ding, Boya Zhang, Rui Liang, Shusen Wang, Zhongyang Shen

BMC endocrine disorders 2021 Mar 12

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NKX6.1 is a transcription factor for insulin, as well as a marker for β cell maturity. Abnormal NKX6.1 expression in β cells, such as translocation from the nucleus to cytoplasm or lost expression, has been shown as a marker for β cell dedifferentiation. We obtained pancreatic sections from organ donors and immunofluorescence staining with NKX6.1 and insulin was performed to characterize NKX6.1 expression in subjects with or without type 2 diabetes mellitus (T2DM). Our results showed that cells with insulin expression but no nucleic NKX6.1 expression (NKX6.1Nuc-Ins+), and cells with cytoplasmic NKX6.1 expression but no insulin expression (NKX6.1cytIns-) were significantly increased in T2DM subjects and positively correlated with glycated hemoglobin (HbA1c), indicating the elevated β cell dedifferentiation with NKX6.1 inactivation in T2DM. To investigate whether β cell dedifferentiation has initiated in subjects with higher risks for T2DM, we next analyzed the association between β-cell dedifferentiation level in ND subjects with different ages, body mass index, and HbA1c. The results showed the absolute number and percentage of dedifferentiated β cells with NKX6.1 inactivation did not significantly change in subjects with advanced aging, obesity, or modest hyperglycemia, indicating that the β cell dedifferentiation might mainly occur after T2DM was diagnosed. Our results suggested that NKX6.1 expression in β cells was changed in type 2 diabetic subjects, evidenced by significantly increased NKX6.1Nuc-Ins+ and NKX6.1cytIns- cells. This abnormality did not occur more frequently in subjects with a higher risk for T2DM, suggesting that β cell dedifferentiation might be secondary to the pathological changes in T2DM.

Citation

Tengli Liu, Peng Sun, Jiaqi Zou, Le Wang, Guanqiao Wang, Na Liu, Yaojuan Liu, Xuejie Ding, Boya Zhang, Rui Liang, Shusen Wang, Zhongyang Shen. Increased frequency of β cells with abnormal NKX6.1 expression in type 2 diabetes but not in subjects with higher risk for type 2 diabetes. BMC endocrine disorders. 2021 Mar 12;21(1):47