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Cited by 102Pancreatic function and diabetesDiabetes and associated disordersEndoplasmic Reticulum Stress and Disease

TGFβ receptor signaling is essential for inflammation-induced but not β-cell workload-induced β-cell proliferation

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Xiao, Xiangwei, Wiersch, John, El-Gohary, Yousef, Guo, Ping, Prasadan, Krishna, Paredes, Jose, Welsh, Carey, Shiota, Chiyo +1 more·2013·Diabetes
DOI 10.2337/db12-1428PMC PMC3609557
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Abstract

Protection and restoration of a functional β-cell mass are fundamental strategies for prevention and treatment of diabetes. Consequently, knowledge of signals that determine the functional β-cell mass is of immense clinical relevance. Transforming growth factor β (TGFβ) superfamily signaling pathways play a critical role in development and tissue specification. Nevertheless, the role of these pathways in adult β-cell homeostasis is not well defined. Here, we ablated TGFβ receptor I and II genes in mice undergoing two surgical β-cell replication models (partial pancreatectomy or partial duct ligation), representing two triggers for β-cell proliferation, increased β-cell workload and local inflammation, respectively. Our data suggest that TGFβ receptor signaling is necessary for baseline β-cell proliferation. By either provision of excess glucose or treatment with exogenous insulin, we further demonstrated that inflammation and increased β-cell workload are both stimulants for β-cell proliferation but are TGFβ receptor signaling dependent and independent, respectively. Collectively, by using a pancreas-specific TGFβ receptor–deleted mouse model, we have identified two distinct pathways that regulate adult β-cell proliferation. Our study thus provides important information for understanding β-cell proliferation during normal growth and in pancreatic diseases.

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  • Tgfb2 is a member of the TGF-β superfamily that signals through Smad transcription factors.

    “Tgfb2 is a member of the TGF-β superfamily of proteins that is involved in diverse roles across different cell types by signaling through a group of transcription factors called Smads [13].”

    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 [13]

    The introductory passage (page unavailable) says TGFβ superfamily signaling has diverse roles across cell types and can activate Smad transcription factors. The References list names TGF-β2 as an isoform, but the paper does not specifically describe Tgfb2 signaling through Smads; that part is inferred from its discussion of the broader family. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • The TGF-β signaling pathway has been implicated in the development of the endocrine pancreas, β-cell development, and postnatal β-cell identity and function.

    “This signaling pathway has also been implicated in the development of the endocrine pancreas [13], β-cell development, and postnatal β-cell identity and function [14].”

    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 [13]

    The paper’s introductory passage (labeled Abstract in our copy; page unavailable) links TGF-β signaling to embryonic endocrine-cell differentiation and maturation, and discusses its effects on β-cell insulin release and proliferation. The Discussion also addresses adult β-cell homeostasis. Neither passage establishes a role in maintaining postnatal β-cell identity, so that part of the claim is unsupported. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Authors
Xiao, X., Wiersch, J., El-Gohary, Y., Guo, P., Prasadan, K., Paredes, J., Welsh, C., Shiota, C., & Gittes, G. K.
Affiliations
  • University of Pittsburgh (US)
  • Division of Pediatric Surgery, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Corresponding author
Gittes, George K.
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2013-03-14
Volume
62
Issue
4
Pages
1217-1226
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db12-1428
PMC
PMC3609557
OpenAlex
W2101526674
Cited by
102
References
3
Citations by year
2026: 1 · 2024: 3 · 2023: 2 · 2022: 8 · 2021: 6 · 2020: 4 · 2019: 6 · 2018: 6 · 2017: 11 · 2016: 10 · 2015: 20 · 2014: 19 · 2013: 6
FWCI
14.70
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
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK064952, R01DK083541)
  • Children's Hospital of Pittsburgh
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 proliferation, pancreatitis, partial pancreatectomy, TGFBR2, glucose, insulin
MeSH terms
Animals, Glucose, Insulin, Male, Mice, Inbred C57BL, Pancreatectomy, RNA-Directed DNA Polymerase, Signal Transduction, Transforming Growth Factor beta, Receptors, Transforming Growth Factor beta, Mice, Knockout, Cell Proliferation, Insulin-Secreting Cells, Mice

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