Cited by 1,078Pancreatic function and diabetesEndoplasmic Reticulum Stress and DiseaseAdvanced Glycation End Products research

Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes

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Robertson, R. Paul·2004·Journal of Biological Chemistry

Abstract

Glucose in chronic excess causes toxic effects on structure and function of organs, including the pancreatic islet. Multiple biochemical pathways and mechanisms of action for glucose toxicity have been suggested. These include glucose autoxidation, protein kinase C activation, methylglyoxal formation and glycation, hexosamine metabolism, sorbitol formation, and oxidative phosphorylation. There are many potential mechanisms whereby excess glucose metabolites traveling along these pathways might cause beta cell damage.

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  • ROS is capable to directly damage β cells, promoting apoptosis, or it can indirectly regulate insulin signaling pathway to inhibit the function of β cells.

    “Therefore, ROS is capable to directly damage β cells, promoting apoptosis, or it can indirectly regulate insulin signaling pathway to inhibit the function of β cells (82, 83).”

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Research works printed but not linked: 8

  1. Inoguchi, T., Battan, R., Handler, E., Sportsman, J. R., Heath, W., and King, G. L. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 11059 -11063
  2. Du, X. L., Edelstein, D., Rossetti, L., Fantus, I. G., Goldberg, H., Ziyadeh, F., Wu, J., and Brownlee, M. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 12222-12226
  3. Olson, L. K., Sharma, A., Peshavaria, M., Wright, C. V., Towle, H. C., Robert- son, R. P., and Stein, R. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 9127-9131
  4. Olbrot, M., Rud, J., Moss, L. G., and Sharma, A. (2002) Proc. Natl. Acad. Sci.
  5. Unger, R. H. (2004) in Diabetes Mellitus: a Fundamental and Clinical Text (LeRoith, D., Olefsky, J., and Taylor, S., eds) 3rd Ed, pp. 141-149, Lippin- cott Williams & Wilkins, Inc., Philadelphia
  6. Tanaka, Y., Tran, P. O., Harmon, J., and Robertson, R. P. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 12363-12368
  7. Kubisch, H. M., Wang, J., Luche, R., Carlson, E., Bray, T. M., Epstein, C. J., and Phillips, J. P. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 9956 -9959
  8. Tanaka, Y., Gleason, C. E., Tran, P. O., Harmon, J. S., and Robertson, R. P. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 10857-10862

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Authors
Robertson, R. P.
Affiliations
University of Washington (US)
Corresponding author
Robertson, R. Paul
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2004-10
Volume
279
Issue
41
Pages
42351-42354
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2152656461
Cited by
1,078
References
60
Citations by year
2026: 35 · 2025: 33 · 2024: 31 · 2023: 37 · 2022: 46 · 2021: 45 · 2020: 39 · 2019: 55 · 2018: 57 · 2017: 57 · 2016: 49 · 2015: 61 · 2014: 70 · 2013: 68 · 2012: 76
FWCI
7.79
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
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 › Clinical Biochemistry › Advanced Glycation End Products research
Keywords
glucotoxicity, pancreatic beta cells, pancreatic islets, oxidative stress, diabetes mellitus, protein kinase C, methylglyoxal, glycation, hexosamine metabolism, sorbitol, oxidative phosphorylation, beta cell destruction
MeSH terms
Animals, Antioxidants, Blood Glucose, Diabetes Mellitus, Gene Expression Regulation, Glucose, Humans, Hyperglycemia, Insulin, Islets of Langerhans, Models, Biological, Reactive Oxygen Species, Oxidative Stress

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