CoChat
Sign Up
Cited by 1,491Pancreatic function and diabetesDiabetes and associated disordersEndoplasmic Reticulum Stress and Disease

Mechanisms of Pancreatic β-Cell Death in Type 1 and Type 2 Diabetes

Cnop, Miriam, Welsh, Nils, Jonas, Jean-Christophe, Jörns, Anne, Lenzen, Sigurd, Eizirik, Decio L.·2005·Diabetes
DOI 10.2337/diabetes.54.suppl_2.s97
Open this paper in CoChat — free account

Abstract

Type 1 and type 2 diabetes are characterized by progressive β-cell failure. Apoptosis is probably the main form of β-cell death in both forms of the disease. It has been suggested that the mechanisms leading to nutrient- and cytokine-induced β-cell death in type 2 and type 1 diabetes, respectively, share the activation of a final common pathway involving interleukin (IL)-1β, nuclear factor (NF)-κB, and Fas. We review herein the similarities and differences between the mechanisms of β-cell death in type 1 and type 2 diabetes. In the insulitis lesion in type 1 diabetes, invading immune cells produce cytokines, such as IL-1β, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. IL-1β and/or TNF-α plus IFN-γ induce β-cell apoptosis via the activation of β-cell gene networks under the control of the transcription factors NF-κB and STAT-1. NF-κB activation leads to production of nitric oxide (NO) and chemokines and depletion of endoplasmic reticulum (ER) calcium. The execution of β-cell death occurs through activation of mitogen-activated protein kinases, via triggering of ER stress and by the release of mitochondrial death signals. Chronic exposure to elevated levels of glucose and free fatty acids (FFAs) causes β-cell dysfunction and may induce β-cell apoptosis in type 2 diabetes. Exposure to high glucose has dual effects, triggering initially “glucose hypersensitization” and later apoptosis, via different mechanisms. High glucose, however, does not induce or activate IL-1β, NF-κB, or inducible nitric oxide synthase in rat or human β-cells in vitro or in vivo in Psammomys obesus. FFAs may cause β-cell apoptosis via ER stress, which is NF-κB and NO independent. Thus, cytokines and nutrients trigger β-cell death by fundamentally different mechanisms, namely an NF-κB–dependent mechanism that culminates in caspase-3 activation for cytokines and an NF-κB–independent mechanism for nutrients. This argues against a unifying hypothesis for the mechanisms of β-cell death in type 1 and type 2 diabetes and suggests that different approaches will be required to prevent β-cell death in type 1 and type 2 diabetes.

Integrity signals

Registry

Crossref · 10.2337/diabetes.54.suppl_2.s97

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Inflammation can be a mediator of insulin resistance and beta-cell damage by high glucose, fatty acids, or adipokines released from adipose tissues.

    “Inflammation can be a mediator of insulin resistance and beta-cell damage by high glucose, fatty acids, or adipokines released from adipose tissues [37–39].”

    From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [39]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Cnop, M., Welsh, N., Jonas, J.-C., Jörns, A., Lenzen, S., & Eizirik, D. L.
Affiliations
  • Université Libre de Bruxelles (BE)
  • Uppsala University (SE)
  • UCLouvain (BE)
  • Centre of Anatomy, Hannover Medical School, Hannover, Germany
  • Medizinische Hochschule Hannover (DE)
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2005-12-01
Volume
54
Issue
suppl_2
Pages
S97-S107
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.54.suppl_2.s97
OpenAlex
W2146561547
Cited by
1,491
References
5
Citations by year
2026: 45 · 2025: 52 · 2024: 58 · 2023: 61 · 2022: 75 · 2021: 78 · 2020: 94 · 2019: 83 · 2018: 80 · 2017: 93 · 2016: 92 · 2015: 110 · 2014: 102 · 2013: 85 · 2012: 74
FWCI
40.41
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
  • Digital Access to Libraries (submittedVersion)
Funders
  • National Institutes of Health (5r21ai055464-02)
  • National Institute of Allergy and Infectious Diseases (1R21AI55464-01)
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
pancreatic beta-cell destruction, beta-cell apoptosis, type 1 diabetes, type 2 diabetes, beta-cell failure, IL-1β, NF-κB, Fas, insulin resistance, high glucose, free fatty acids, endoplasmic reticulum stress, nitric oxide, caspase-3, cytokines, endoplasmic reticulum calcium depletion, chemokines
MeSH terms
Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Interferon-gamma, Interleukin-1, Models, Biological, Cell Death, Insulin-Secreting Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review