Dataset Information

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

ABSTRACT:

Background

NKX6.1 is a transcription factor for insulin, as well as a marker for ? cell maturity. Abnormal NKX6.1 expression in ? cells, such as translocation from the nucleus to cytoplasm or lost expression, has been shown as a marker for ? cell dedifferentiation.

Methods

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).

Results

Our results showed that cells with insulin expression but no nucleic NKX6.1 expression (NKX6.1^Nuc-Ins⁺), and cells with cytoplasmic NKX6.1 expression but no insulin expression (NKX6.1^cytIns^-) were significantly increased in T2DM subjects and positively correlated with glycated hemoglobin (HbA1c), indicating the elevated ? cell dedifferentiation with NKX6.1 inactivation in T2DM. To investigate whether ? cell dedifferentiation has initiated in subjects with higher risks for T2DM, we next analyzed the association between ?-cell dedifferentiation level in ND subjects with different ages, body mass index, and HbA1c. The results showed the absolute number and percentage of dedifferentiated ? cells with NKX6.1 inactivation did not significantly change in subjects with advanced aging, obesity, or modest hyperglycemia, indicating that the ? cell dedifferentiation might mainly occur after T2DM was diagnosed.

Conclusion

Our results suggested that NKX6.1 expression in ? cells was changed in type 2 diabetic subjects, evidenced by significantly increased NKX6.1^Nuc-Ins⁺ and NKX6.1^cytIns^- cells. This abnormality did not occur more frequently in subjects with a higher risk for T2DM, suggesting that ? cell dedifferentiation might be secondary to the pathological changes in T2DM.

SUBMITTER: Liu T

PROVIDER: S-EPMC7955633 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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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.

Liu Tengli T Sun Peng P Zou Jiaqi J Wang Le L Wang Guanqiao G Liu Na N Liu Yaojuan Y Ding Xuejie X Zhang Boya B Liang Rui R Wang Shusen S Shen Zhongyang Z

BMC endocrine disorders 20210312 1

<h4>Background</h4>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.<h4>Methods</h4>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 (T2D ...[more]

PMID: 33711989

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