β Cell Aging Markers Have Heterogeneous Distribution and Are Induced by Insulin Resistance
Open accessAbstract
We hypothesized that the known heterogeneity of pancreatic β cells was due to subpopulations of β cells at different stages of their life cycle with different functional capacities and that further changes occur with metabolic stress and aging. We identified new markers of aging in β cells, including IGF1R. In β cells IGF1R expression correlated with age, dysfunction, and expression of known age markers p16 ink4a, p53BP1, and senescence-associated β-galactosidase. The new markers showed striking heterogeneity both within and between islets in both mouse and human pancreas. Acute induction of insulin resistance with an insulin receptor antagonist or chronic ER stress resulted in increased expression of aging markers, providing insight into how metabolic stress might accelerate dysfunction and decline of β cells. These novel findings about β cell and islet heterogeneity, and how they change with age, open up an entirely new set of questions about the pathogenesis of type 2 diabetes.
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The sample sizes used are similar to those in the authors' earlier publications.
“No statistical methods were used to predetermine sample sizes, but our sample sizes are similar to those reported in our previous publications8,22,49.”
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- Authors
- Aguayo-Mazzucato, C., van Haaren, M., Mruk, M., Lee, T. B., Crawford, C., Hollister-Lock, J., Sullivan, B. A., Johnson, J. W., Ebrahimi, A., Dreyfuss, J. M., Van Deursen, J., Weir, G. C., & Bonner-Weir, S.
- Affiliations
- Joslin Diabetes Center (US)
- Boston University (US)
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 25
- Issue
- 4
- Pages
- 898-910.e5
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5471618
- OpenAlex
- W2604579271
- Cited by
- 198
- References
- 66
- Citations by year
- 2026: 9 · 2025: 25 · 2024: 19 · 2023: 26 · 2022: 20 · 2021: 25 · 2020: 24 · 2019: 25 · 2018: 19 · 2017: 6
- FWCI
- 20.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- NIH (R01 DK093909, P30 DK036836, P30 DK057521)
- Diabetes Research and Wellness Foundation
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- beta-cell heterogeneity, IGF-1 receptor, insulin resistance, islet heterogeneity, cellular senescence, p16INK4a, senescence-associated β-galactosidase, endoplasmic reticulum stress, insulin receptor antagonist, type 2 diabetes pathogenesis, metabolic stress
- MeSH terms
- Tumor Suppressor p53-Binding Protein 1, Adolescent, Adult, Aged, Aging, Animals, Diabetes Mellitus, Type 2, Female, Flow Cytometry, Glucose, Hemolytic Plaque Technique, Humans, Insulin, Insulin Resistance, Male, Mice, Inbred C57BL, Middle Aged, RNA, Messenger, Stress, Physiological, Biomarkers, Cellular Senescence, Receptor, IGF Type 1, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Insulin-Secreting Cells, Young Adult
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