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Cited by 68Pancreatic function and diabetesDiabetes and associated disordersEndoplasmic Reticulum Stress and Disease

Maintenance of β-Cell Maturity and Plasticity in the Adult Pancreas

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Szabat, Marta, Lynn, Francis C., Hoffman, Brad G., Kieffer, Timothy J., Allan, Douglas W., Johnson, James D.·2012·Diabetes
DOI 10.2337/db11-1361PMC PMC3357305
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Abstract

Diabetes occurs when the pancreas fails to produce and secrete sufficient insulin for the maintenance of glucose homeostasis. Although many factors required for β-cell development have been elucidated, we know surprisingly little regarding the mechanisms that maintain the differentiated state of adult β-cells. Despite years of fruitful research, many hurdles remain before we can replace failing β-cells in patients. Efforts to produce new β-cells will benefit from detailed knowledge of their differentiation, maturation, maintenance, heterogeneity, and plasticity. Studies of single cells and conditional knockout mice reveal surprising relationships between the different islet cell types and previously unappreciated roles for transcription factors and soluble factors in β-cell maintenance. Herein we highlight numerous innovative efforts made to identify the core mechanisms responsible for β-cell phenotypic maintenance and compare these with other long-lived cell types. In the adult pancreas, physical β-cell mass is determined by the balance of β-cell birth, differentiation, size, and death. The prenatal origins and development of β-cells (1,2), the molecular mechanisms of adult β-cell proliferation (3,4), and programmed β-cell death (5) have all been reviewed recently and will not be revisited here. The maintenance and adaptation of β-cell mass after birth involves the addition of new β-cells (6). Cells with robust staining for insulin have been shown to slowly proliferate in vivo and in vitro (7–9). It has been reported that β-cells have an extremely long life span under typical conditions and proliferation plays a diminishing role with advancing age (7,10,11). The apparent low rate of β-cell replication has led some groups to suggest that adult β-cells arise from a pool of non–β-cell progenitors (12). Because this topic has been hotly debated and reviewed recently (13), we will only briefly discuss studies relevant to other aspects of this review. …

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  • Prior studies have linked loss of β-cell identity and dedifferentiation to β-cell dysfunction in models of insulin resistance and reduced islet mass.

    “Prior studies have linked loss of β-cell identity and dedifferentiation to β-cell dysfunction in models of insulin resistance and reduced islet mass [38, 40].”

    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 [40]

    The section “Active Maintenance of β-Cell Function: Evidence from Conditional Mutants and Human Genetics” (page unavailable) links impaired β-cell function to loss of identity markers after Pdx1 deletion and reports a 40% loss of β-cell mass. It does not establish this link in models of insulin resistance or models defined by pre-existing reduced islet mass; its discussion of lineage confusion is also more specific than a general finding of dedifferentiation. (LLM, conf=0.85)

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Cited by

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Authors
Szabat, M., Lynn, F. C., Hoffman, B. G., Kieffer, T. J., Allan, D. W., & Johnson, J. D.
Affiliations
University of British Columbia (CA)
Corresponding author
Johnson, James D.
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2012-05-14
Volume
61
Issue
6
Pages
1365-1371
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db11-1361
PMC
PMC3357305
OpenAlex
W2104202449
Cited by
68
References
4
Citations by year
2026: 3 · 2025: 1 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 7 · 2018: 8 · 2017: 6 · 2016: 7 · 2015: 11 · 2014: 9 · 2013: 6
FWCI
1.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Keywords
beta cell plasticity, beta cell maturation, beta-cell heterogeneity, beta cell differentiation, beta-cell proliferation, beta-cell death, beta-cell mass, islet cell types, transcription factors, soluble factors, beta cell replacement, adult pancreas
MeSH terms
Adult, Animals, Humans, Pancreas, Developmental Biology, Insulin-Secreting Cells

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