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Cited by 223

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Ubiquitinated-Protein Aggregates Form in Pancreatic β-Cells During Diabetes-Induced Oxidative Stress and Are Regulated by Autophagy

Kaniuk, Natalia A., Kiraly, Michael, Bates, Holly, Vranic, Mladen, Volchuk, Allen, Brumell, John H.·2007·Diabetes
DOI 10.2337/db06-1160
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Abstract

Diabetes-induced oxidative stress can lead to protein misfolding and degradation by the ubiquitin-proteasome system. This study examined protein ubiquitination in pancreatic sections from Zucker diabetic fatty rats. We observed large aggregates of ubiquitinated proteins (Ub-proteins) in insulin-expressing β-cells and surrounding acinar cells. The formation of these aggregates was also observed in INS1 832/13 β-cells after exposure to high glucose (30 mmol/l) for 8–72 h, allowing us to further characterize this phenotype. Oxidative stress induced by aminotriazole (ATZ) was sufficient to stimulate Ub-protein aggregate formation. Furthermore, the addition of the antioxidants N-acetyl cysteine (NAC) and taurine resulted in a significant decrease in formation of Ub-protein aggregates in high glucose. Puromycin, which induces defective ribosomal product (DRiP) formation was sufficient to induce Ub-protein aggregates in INS1 832/13 cells. However, cycloheximide (which blocks translation) did not impair Ub-protein aggregate formation at high glucose levels, suggesting that long-lived proteins are targeted to these structures. Clearance of Ub-protein aggregates was observed during recovery in normal medium (11 mmol/l glucose). Despite the fact that 20S proteasome was localized to Ub-protein aggregates, epoxomicin treatment did not affect clearance, indicating that the proteasome does not degrade proteins localized to these structures. The autophagy inhibitor 3MA blocked aggregate clearance during recovery and was sufficient to induce their formation in normal medium. Together, these findings demonstrate that diabetes-induced oxidative stress induces ubiquitination and storage of proteins into cytoplasmic aggregates that do not colocalize with insulin. Autophagy, not the proteasome, plays a key role in regulating their formation and degradation. To our knowledge, this is the first demonstration that autophagy acts as a defense to cellular damage incurred during diabetes.

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Metadata

Authors
Kaniuk, N. A., Kiraly, M., Bates, H., Vranic, M., Volchuk, A., & Brumell, J. H.
Venue
Diabetes
Publisher
American Diabetes Association
Published
2007-04-01
Volume
56
Issue
4
Pages
930-939
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db06-1160
OpenAlex
W2139941678
Cited by
223
References
8
FWCI
11.93
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Ubiquitinated-Protein Aggregates Form in Pancreatic β-Cells During Diabetes-Induced Oxidative Stress and Are Regulated by Autophagy. https://app.cochat.ai/papers/10.2337/db06-1160
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Kaniuk, N. A., Kiraly, M., Bates, H., Vranic, M., Volchuk, A., & Brumell, J. H. (2007). Ubiquitinated-Protein Aggregates Form in Pancreatic β-Cells During Diabetes-Induced Oxidative Stress and Are Regulated by Autophagy. Diabetes. https://doi.org/10.2337/db06-1160

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