2037-P: Islet ß-Cell Dedifferentiation Is Involved in Progression of Type 2 Diabetes

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2037-P
Author(s):  
KIKUKO AMO-SHIINOKI ◽  
KATSUYA TANABE ◽  
RYOTARO BOUCHI ◽  
WATARU NISHIMURA ◽  
YOSHIHIRO OGAWA ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Dedifferentiation

scholarly journals Evidence of β-Cell Dedifferentiation in Human Type 2 Diabetes

2016 ◽  
Vol 101 (3) ◽  
pp. 1044-1054 ◽  
Author(s):  
Francesca Cinti ◽  
Ryotaro Bouchi ◽  
Ja Young Kim-Muller ◽  
Yoshiaki Ohmura ◽  
P. R. Sandoval ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
Human Type

Beta-Cell Dedifferentiation and Type 2 Diabetes

2013 ◽  
Vol 368 (6) ◽  
pp. 572-573 ◽  
Author(s):  
Yuval Dor ◽  
Benjamin Glaser
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Cell Dedifferentiation

scholarly journals Salsalate Prevents β-Cell Dedifferentiation in OLETF Rats with Type 2 Diabetes through Notch1 Pathway

2019 ◽  
Vol 10 (4) ◽  
pp. 719 ◽  
Author(s):  
Fei Han ◽  
Xiaochen Li ◽  
Juhong Yang ◽  
Haiyi Liu ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
Oletf Rats

scholarly journals A Brief Review of the Mechanisms of β-Cell Dedifferentiation in Type 2 Diabetes

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1593
Author(s):  
Phyu-Phyu Khin ◽  
Jong-Han Lee ◽  
Hee-Sook Jun
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Cell Mass ◽  
Cell Loss ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
Glucose Levels ◽  
Β Cell Function ◽  
Dedifferentiation Process

Diabetes is a metabolic disease characterized by hyperglycemia. Over 90% of patients with diabetes have type 2 diabetes. Pancreatic β-cells are endocrine cells that produce and secrete insulin, an essential endocrine hormone that regulates blood glucose levels. Deficits in β-cell function and mass play key roles in the onset and progression of type 2 diabetes. Apoptosis has been considered as the main contributor of β-cell dysfunction and decrease in β-cell mass for a long time. However, recent studies suggest that β-cell failure occurs mainly due to increased β-cell dedifferentiation rather than limited β-cell proliferation or increased β-cell death. In this review, we summarize the current advances in the understanding of the pancreatic β-cell dedifferentiation process including potential mechanisms. A better understanding of β-cell dedifferentiation process will help to identify novel therapeutic targets to prevent and/or reverse β-cell loss in type 2 diabetes.

scholarly journals 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

2020 ◽  
Author(s):  
Tengli Liu ◽  
Peng Sun ◽  
Jiaqi Zou ◽  
Le Wang ◽  
Guanqiao Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycated Hemoglobin ◽  
Absolute Number ◽  
Organ Donors ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
Insulin Expression ◽  
Type 2 Diabetic

Abstract 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: Here, we obtained pancreata sections from organ donors, and aim to characterize NKX6.1 expression in subjects with or without type 2 diabetes mellitus (T2DM), and NKX6.1 and insulin immunofluorescence staining was performed. 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 may mainly occur after T2DM was diagnosed. Conclusion: In sum, our results suggested that NKX6.1 expression in β cells is changed in type 2 diabetic subjects, evidenced by significantly increased NKX6.1Nuc-Ins+ and NKX6.1cytIns- cells. This abnormality does 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.

scholarly journals The Anna Karenina model of β cell maturation in development and their dedifferentiation in type 1 and type 2 diabetes

2021 ◽  
Author(s):  
Sutichot D. Nimkulrat ◽  
Zijian Ni ◽  
Jared Brown ◽  
Christina Kendziorski ◽  
Barak Blum
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Lineage Tracing ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
Anna Karenina ◽  
Β Cell Function

AbstractLoss of mature β cell function and identity, or β cell dedifferentiation, is seen in all types of diabetes mellitus. Two competing models explain β cell dedifferentiation in diabetes. In the first model, β cells dedifferentiate in the reverse order of their developmental ontogeny. This model predicts that dedifferentiated β cells resemble β cell progenitors. In the second model, β cell dedifferentiation depends on the type of diabetogenic stress. This model, which we call the “Anna Karenina” model, predicts that in each type of diabetes, β cells dedifferentiate in their own way, depending on how their mature identity is disrupted by any particular diabetogenic stress. We directly tested the two models using a β cell-specific lineage-tracing system coupled with RNA-sequencing in mice. We constructed a multidimensional map of β cell transcriptional trajectories during the normal course of β cell postnatal development and during their dedifferentiation in models of both type 1 diabetes (NOD) and type 2 diabetes (BTBR-Lepob/ob). Using this unbiased approach, we show here that despite some similarities between immature and dedifferentiated β cells, β cells dedifferentiation in the two mouse models is not a reversal of developmental ontogeny and is different between different types of diabetes.

scholarly journals 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

2020 ◽  
Author(s):  
Tengli Liu ◽  
Peng Sun ◽  
Jiaqi Zou ◽  
Le Wang ◽  
Guanqiao Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycated Hemoglobin ◽  
Absolute Number ◽  
Organ Donors ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
Insulin Expression ◽  
Type 2 Diabetic

Abstract 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: Here, we obtained pancreata sections from organ donors, and aim to characterize NKX6.1 expression in subjects with or without type 2 diabetes mellitus (T2DM), and NKX6.1 and insulin immunofluorescence staining was performed.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 cyt Ins - ) 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 may mainly occur after T2DM was diagnosed.Conclusion: In sum, our results suggested that NKX6.1 expression in β cells is changed in type 2 diabetic subjects, evidenced by significantly increased NKX6.1 Nuc- Ins + and NKX6.1 cyt Ins - cells. This abnormality does 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.

scholarly journals The Anna Karenina Model of β Cell Maturation in Development and their Dedifferentiation in Type 1 and Type 2 Diabetes

2021 ◽  
Author(s):  
Sutichot D. Nimkulrat ◽  
Matthew N. Bernstein ◽  
Zijian Ni ◽  
Jared Brown ◽  
Christina Kendziorski ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Lineage Tracing ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
Anna Karenina ◽  
Β Cell Function

Loss of mature β cell function and identity, or β cell dedifferentiation, is seen in both type 1 and type 2 diabetes. Two competing models explain β cell dedifferentiation in diabetes. In the first model, β cells dedifferentiate in the reverse order of their developmental ontogeny. This model predicts that dedifferentiated β cells resemble β cell progenitors. In the second model, β cell dedifferentiation depends on the type of diabetogenic stress. This model, which we call the “Anna Karenina” model, predicts that in each type of diabetes, β cells dedifferentiate in their own way, depending on how their mature identity is disrupted by any particular diabetogenic stress. We directly tested the two models using a β cell-specific lineage-tracing system coupled with RNA-sequencing in mice. We constructed a multidimensional map of β cell transcriptional trajectories during the normal course of β cell postnatal development and during their dedifferentiation in models of both type 1 diabetes (NOD) and type 2 diabetes (BTBR-<i>Lep<sup>ob/ob</sup></i>). Using this unbiased approach, we show here that despite some similarities between immature and dedifferentiated β cells, <a>β cells dedifferentiation in the two mouse models is not a reversal of developmental ontogeny and is different between </a>different types of diabetes.

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