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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
Rui Liang
Tianjin First Central Hospital
Corresponding Author
Shusen Wang
Tianjin First Central Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2323-6564
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Background: 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.
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 (NKX6.1Nuc-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.
Conclusion: 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.
Keywords
NKX6.1, Age, Obesity, HbA1c, β-cell dedifferentiation
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Editorial decision: Minor revision
On 06 Jan, 2021
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Invitations sent on 30 Nov, 2020
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Editorial decision: Major revision
On 30 Sep, 2020
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Received 28 Sep, 2020
Reviewer #2 agreed
On 08 Sep, 2020
Review #1 received
Received 29 Aug, 2020
Reviewer #1 agreed
On 27 Aug, 2020
Reviewers invited
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First submitted
On 20 Jul, 2020
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On 19 Jul, 2020
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Subject Areas
Endocrinology & Metabolism
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This preprint is under consideration at BMC Endocrine Disorders. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
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
Rui Liang
Tianjin First Central Hospital
Corresponding Author
Shusen Wang
Tianjin First Central Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2323-6564
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 3
Posted 22 Dec, 2020
No community comments so far
Editorial decision: Minor revision
On 06 Jan, 2021
Editor assigned
On 06 Dec, 2020
Submission checks complete
On 06 Dec, 2020
Editor invited
On 06 Dec, 2020
No comments provided
Reviewers invited
Invitations sent on 30 Nov, 2020
Editor assigned
On 24 Nov, 2020
Submission checks complete
On 24 Nov, 2020
Editor invited
On 24 Nov, 2020
No comments provided
Editorial decision: Major revision
On 30 Sep, 2020
Review #2 received
Received 28 Sep, 2020
Reviewer #2 agreed
On 08 Sep, 2020
Review #1 received
Received 29 Aug, 2020
Reviewer #1 agreed
On 27 Aug, 2020
Reviewers invited
Invitations sent on 19 Aug, 2020
First submitted
On 20 Jul, 2020
Editor assigned
On 20 Jul, 2020
Submission checks complete
On 19 Jul, 2020
Editor invited
On 19 Jul, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Endocrinology & Metabolism
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: 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.
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 (NKX6.1Nuc-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.
Conclusion: 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.
Figure 1
Figure 2