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Cited by 386Endoplasmic Reticulum Stress and DiseasePancreatic function and diabetesIon Channels and Receptors

Endoplasmic reticulum stress and pancreatic β-cell death

Open access
Fonseca, Sonya G., Gromada, Jesper, Urano, Fumihiko·2011·Trends in Endocrinology & Metabolism
DOI 10.1016/j.tem.2011.02.008PMC PMC3130122
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Abstract

In pancreatic β-cells, the endoplasmic reticulum (ER) is an important cellular compartment for insulin biosynthesis, which accounts for half of the total protein production in these cells. Protein flux through the ER must be carefully monitored to prevent dysregulation of ER homeostasis and stress. ER stress elicits a signaling cascade known as the unfolded protein response (UPR), which influences both life and death decisions in cells. β-cell loss is a pathological component of both type 1 and type 2 diabetes, and recent findings suggest that ER stress is involved. In this review, we address the transition from the physiological ER stress response to the pathological response, and explore the mechanisms of ER stress-mediated β-cell loss during the progression of diabetes.

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Crossref · 10.1016/j.tem.2011.02.008

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  • Over time, recurrent postprandial hyperglycemia and prolonged insulin secretion may promote β-cell stress and accelerate progression from impaired glucose tolerance to overt T2D.

    “Over time, both mechanisms, recurrent postprandial hyperglycemia and prolonged insulin secretion, may promote β-cell stress and accelerate progression from impaired glucose tolerance to overt T2D (34,35).”

    From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With <i>MTNR1B</i> Diabetes Risk Variant (2026) · cites this paper as [34]

    In “Causes of ER-stressed β cells” (page unavailable), the paper says high glucose and increased insulin biosynthesis can cause β-cell ER stress. In “ER stress: Link between β cell loss and impaired function in common forms of diabetes” (page unavailable), it proposes that this stress contributes to the transition from pre-diabetes to overt diabetes. It does not specifically establish recurrent postprandial hyperglycemia, prolonged insulin secretion, or progression from impaired glucose tolerance; its clinical example concerns impaired fasting glucose. (LLM, conf=0.85)

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  • Elevated melatonin in the presence of food intake may represent an additional path to prolonged insulin secretion, which may cause endoplasmic reticulum stress in β-cells and ultimately lead to β-cell failure.

    “Accordingly, elevated melatonin in the presence of food intake may represent an additional path to prolonged insulin secretion, which may cause endoplasmic reticulum stress in β-cells and ultimately lead to β-cell failure (34).”

    From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With <i>MTNR1B</i> Diabetes Risk Variant (2026) · cites this paper as [34]

    The 'Causes of ER-stressed β cells' section says that increased insulin biosynthesis under high glucose can overwhelm ER folding capacity, leading to stress, dysfunction and death. The 'Protein homeostasis in the β cell' section also links insulin demand to ER stress. Neither passage addresses elevated melatonin during food intake or shows that it prolongs insulin secretion; that proposed route is not supported by this source. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Inflammatory cytokines, hypoxia, and hyperglycemia can all induce an ER stress response in β cells that leads to cell dysfunction and apoptosis.

    “Inflammatory cytokines, hypoxia, and hyperglycemia can all induce an ER stress response in β cells that leads to cell dysfunction and apoptosis.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [127]

    The “Causes of ER-stressed β cells” section says that inflammatory cytokines, hypoxia, and high glucose can each induce ER stress. It links chronic high glucose to β-cell dysfunction and death, but says ER stress–mediated death from cytokines is controversial and describes the link between hypoxia-mediated ER stress and apoptosis as a possibility, not an established outcome for all exposed cells. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Perturbations in normal metabolism and environmental conditions can induce endoplasmic reticulum (ER) stress and initiate the unfolded protein response (UPR).

    “Perturbations in normal metabolism and environmental conditions can induce endoplasmic reticulum (ER) stress and initiate the unfolded protein response (UPR).”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [127]

  • The UPR aims to restore protein homeostasis under mild stress conditions but will induce apoptosis if the trigger is more severe.

    “While this pathway aims to restore protein homeostasis under mild stress conditions, it will induce apoptosis if the trigger is more severe.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [127]

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Research works printed but not linked: 1

  1. [25]Robertson RP LeRoith D Glucose toxicity of the beta-cell Diabetes Mellitus 2004 Lippincott Williams & Wilkins 129 139

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Authors
Fonseca, S. G., Gromada, J., & Urano, F.
Affiliations
University of Massachusetts Chan Medical School (US)
ORCID
Venue
Trends in Endocrinology & Metabolism
Publisher
Elsevier BV
Published
2011-03
Volume
22
Issue
7
Pages
266-74
ISSN
1043-2760 (ISSN-L)
DOI
10.1016/j.tem.2011.02.008
PMC
PMC3130122
OpenAlex
W2039420809
Cited by
384
References
100
Citations by year
2026: 7 · 2025: 14 · 2024: 20 · 2023: 30 · 2022: 34 · 2021: 34 · 2020: 28 · 2019: 35 · 2018: 18 · 2017: 31 · 2016: 23 · 2015: 27 · 2014: 32 · 2013: 21 · 2012: 24
FWCI
2.26
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Trends in Endocrinology and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK067493, 5 P30 DK 32520, P30DK032520)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords
endoplasmic reticulum stress, pancreatic beta cells, beta-cell death, unfolded protein response, insulin biosynthesis, type 1 diabetes, type 2 diabetes, ER homeostasis, diabetes pathogenesis
MeSH terms
Animals, Diabetes Mellitus, Endoplasmic Reticulum, Humans, Stress, Physiological, Protein Biosynthesis, Cell Death, Oxidative Stress, Disease Progression, Insulin-Secreting Cells, Unfolded Protein Response, Molecular Targeted Therapy

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