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Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes
Abu Saleh Md Moin1, Alexandra E Butler2
1Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, PO Box 34110, Doha, Qatar.
Current Diabetes Reports
|August 12, 2019
Summary
Pancreatic beta cells in diabetes can lose their identity through dedifferentiation or transdifferentiation, altering their function and marker expression. In humans, "altered identity" is preferred due to unclear cellular fate.
Area of Science:
- Endocrinology
- Cell Biology
- Diabetes Research
Background:
- Pancreatic beta cells are crucial for glucose homeostasis.
- Diabetes is characterized by beta cell dysfunction and loss.
- Altered beta cell identity is a proposed mechanism in diabetes pathogenesis.
Purpose of the Study:
- To review the current understanding of beta cell identity.
- To explore factors causing altered beta cell identity in diabetes, particularly in humans.
Main Methods:
- Review of existing literature on beta cell dedifferentiation and transdifferentiation.
- Analysis of gene expression changes in beta cells in diabetic models and human subjects.
- Examination of cellular fate and marker expression in altered beta cells.
Main Results:
- Beta cell identity loss involves decreased expression of key markers (e.g., MafA, NeuroD1) and increased expression of atypical genes.
- Transdifferentiation can lead to beta cells becoming other islet cell types (e.g., alpha cells).
- Human studies show alpha-beta double-positive cells in type 2 diabetes (T2D), supporting altered identity.
Conclusions:
- Altered beta cell identity may be a compensatory or regenerative response to stress or injury in diabetes.
- In humans, "altered identity" is more accurate than dedifferentiation due to uncertain cellular fate.
- Beta cell identity changes recapitulate less mature cell types, potentially as an adaptive mechanism.
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