Pancreatic β-cell identity in diabetes

Remedi, M. S.; Emfinger, C.

doi:10.1111/dom.12727

Cited by 128Pancreatic function and diabetesDiabetes and associated disordersDiabetes Treatment and Management

Pancreatic β-cell identity in diabetes

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Remedi, M. S., Emfinger, C.·2016·Diabetes, Obesity and Metabolism

DOI 10.1111/dom.12727PMC PMC5021188

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Abstract

Recovery of functional β‐cell mass continues to be an ongoing challenge in treating diabetes. Initial work studying β‐cells suggested apoptotic β‐cell death as a main contributor for the loss of β‐cell mass in diabetes. Restoration of β‐cells either by transplant or stimulating proliferation of remaining β‐cells or precursors would then logically be a viable therapeutic option for diabetes. However, recent work has highlighted the inherent β‐cell plasticity and the critical role of loss of β‐cell identity in diabetes, and has suggested that β‐cells fail to maintain a fully differentiated glucose‐responsive and drug‐responsive state, particularly in diabetic individuals with poorly controlled, long‐lasting periods of hyperglycaemia. Understanding the underlying mechanisms of loss of β‐cell identity and conversion in other cell types, as well as how to regain their mature differentiated functional state, is critical to develop novel therapeutic strategies to prevent or reverse these processes. In this review, we discuss the role of plasticity and loss of β‐cell identity in diabetes, the current understanding of mechanisms involved in altering this mature functional β‐cell state and potential progresses to identify novel therapeutic targets providing better opportunities for slowing or preventing diabetes progression.

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β-cell dedifferentiation, loss of identity, or reversion to a progenitor-like state is a compensatory response to islet inflammatory stress, with evidence in models of T1D and T2D.
“Recent data have identified β-cell dedifferentiation, loss of identity, or reversion to a progenitor-like state, as a compensatory response to islet inflammatory stress, with evidence of β-cell dedifferentiation in models of T1D and T2D [35].”
From β-Cell pre-mir-21 induces dysfunction and loss of cellular identity by targeting transforming growth factor beta 2 (Tgfb2) and Smad family member 2 (Smad2) mRNAs (2021) · cites this paper as [35]
In “Is it a change in β-cell fate in diabetes?” (page unavailable), the paper describes loss of β-cell identity and reversion to progenitor-like cells, and reports evidence in type 2 diabetes. The Concluding remarks (page unavailable) propose dedifferentiation as a possible protective response to metabolic stress, not specifically islet inflammatory stress. The paper says dedifferentiation may occur in type 1 diabetes, but the cited passages do not establish evidence in a type 1 diabetes model. (LLM, conf=0.88)
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Authors: Remedi, M. S., & Emfinger, C.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Remedi, M. S.
ORCID: Remedi, M. S.
Emfinger, C.
Venue: Diabetes, Obesity and Metabolism
Publisher: Wiley
Published: 2016-09
Volume: 18
Issue: S1
Pages: 110-116
ISSN: 1462-8902 (ISSN-L)
1463-1326
DOI: 10.1111/dom.12727
PMC: PMC5021188
OpenAlex: W2518974058
Cited by: 128
References: 80
Citations by year: 2026: 7 · 2025: 5 · 2024: 15 · 2023: 16 · 2022: 26 · 2021: 25 · 2020: 11 · 2019: 12 · 2018: 5 · 2017: 5 · 2016: 1
FWCI: 1.52
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 11 d)
Locations: Diabetes Obesity and Metabolism (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (R01 DK098584)
Diabetes Research Center (5P60 DK020579)
Topics: Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: beta cell plasticity, beta cell differentiation, beta-cell mass loss, beta-cell apoptosis, hyperglycemia, glucose responsiveness, drug response, diabetes treatment, beta cell regeneration
MeSH terms: Cell Plasticity, Insulin Secretion, Animals, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Insulin, Regeneration, Disease Progression, Cell Proliferation, Insulin-Secreting Cells, Mice, Cell Dedifferentiation, Cell Transdifferentiation

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Pancreatic β-cell identity in diabetes

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