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Cited by 95Pancreatic function and diabetesEndoplasmic Reticulum Stress and DiseaseDiabetes and associated disorders

Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis

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Kulkarni, Abhishek, Muralidharan, Charanya, May, Sarah C, Tersey, Sarah A, Mirmira, Raghavendra G·2022·Endocrinology
DOI 10.1210/endocr/bqac184PMC PMC9667558
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Abstract

The pathogeneses of the 2 major forms of diabetes, type 1 and type 2, differ with respect to their major molecular insults (loss of immune tolerance and onset of tissue insulin resistance, respectively). However, evidence suggests that dysfunction and/or death of insulin-producing β-cells is common to virtually all forms of diabetes. Although the mechanisms underlying β-cell dysfunction remain incompletely characterized, recent years have witnessed major advances in our understanding of the molecular pathways that contribute to the demise of the β-cell. Cellular and environmental factors contribute to β-cell dysfunction/loss through the activation of molecular pathways that exacerbate endoplasmic reticulum stress, the integrated stress response, oxidative stress, and impaired autophagy. Whereas many of these stress responsive pathways are interconnected, their individual contributions to glucose homeostasis and β-cell health have been elucidated through the development and interrogation of animal models. In these studies, genetic models and pharmacological compounds have enabled the identification of genes and proteins specifically involved in β-cell dysfunction during diabetes pathogenesis. Here, we review the critical stress response pathways that are activated in β cells in the context of the animal models.

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  • Hypoxic conditions and oxidative stress can also induce other stress pathways that result in β cell functional failure and apoptosis.

    “Hypoxic conditions and oxidative stress can also induce other stress pathways that result in β cell functional failure and apoptosis.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [134]

    The “Oxidative Stress in β-Cell Dysfunction” section says oxidative stress can lead to ER stress and that ROS can activate pathways that trigger β-cell apoptosis. The Conclusions also link prolonged stress-pathway activation to β-cell dysfunction and death. The passages found do not address hypoxic conditions as a trigger, so that part of the claim is unsupported by our copy. (LLM, conf=0.84)

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Authors
Kulkarni, A., Muralidharan, C., May, S. C., Tersey, S. A., & Mirmira, R. G.
Affiliations
University of Chicago (US)
Corresponding author
Mirmira, Raghavendra G
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2022-11-01
Volume
164
Issue
1
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/endocr/bqac184
PMC
PMC9667558
OpenAlex
W4307842291
Cited by
95
References
222
Citations by year
2026: 31 · 2025: 26 · 2024: 22 · 2023: 15 · 2022: 1
FWCI
3.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Endocrinology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (U01 DK127786, R01 DK124906, R01 DK060581, R01 DK105588, P30 DK020595)
  • University of Chicago
  • Diabetes Research Connection
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
beta-cell dysfunction, beta-cell death, endoplasmic reticulum stress, integrated stress response, oxidative stress, autophagy, type 1 diabetes, type 2 diabetes, diabetes pathogenesis, glucose homeostasis, animal models of diabetes
MeSH terms
Animals, Autophagy, Diabetes Mellitus, Type 2, Insulin Resistance, Oxidative Stress, Insulin-Secreting Cells, Endoplasmic Reticulum Stress

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