Carbonyl reductase 1 protects pancreatic β-cells against oxidative stress-induced apoptosis in glucotoxicity and glucolipotoxicity

M. A. Rashid, Seonmin Lee, Eunyoung Tak, Jisun Lee, Tae Gyu Choi, Joo Won Lee, Jae Bum Kim, Jang H. Youn, Insug Kang, Joohun Ha, Sung Soo Kim

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Carbonyl reductase 1 (CBR1) plays an important role in the detoxification of reactive lipid aldehydes. Oxidative stress has been implicated in the pathogenesis of pancreatic β-cell failure. However, the functional role of CBR1 in pancreatic β-cell failure has not been studied yet. Therefore, we investigated the role of CBR1 in pancreatic β-cell failure under glucotoxic and glucolipotoxic conditions. Under both conditions, knockdown of CBR1 by specific siRNA increased β-cell apoptosis, expression of lipogenic enzymes (such as ACC, FAS, and ABCA1), intracellular lipid accumulation, oxidative stress, ER stress, and nuclear SREBP1c, but decreased glucose-stimulated insulin secretion. In contrast, overexpression of CBR1 showed the opposite effects. The antioxidants N-acetyl- l-cysteine and Tiron, as well as the FAS inhibitor cerulenin, reversed the effects of CBR1 knockdown. Interestingly, the expression level and enzyme activity of CBR1 were significantly decreased in pancreatic islets of db/db mice, compared with those of wild-type mice. In conclusion, CBR1 protects pancreatic β-cells against oxidative stress and promotes their survival in glucotoxicity and glucolipotoxicity.

Original languageEnglish (US)
Pages (from-to)1522-1533
Number of pages12
JournalFree Radical Biology and Medicine
Volume49
Issue number10
DOIs
StatePublished - Nov 30 2010

Bibliographical note

Funding Information:
We are grateful to Dr. Byung-Hyun Park at Chonbuk National University for critically reading our manuscript. This work was supported by Korea Science and Engineering Foundation Grant 20090091346 to S.S. Kim from the Korea government.

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

  • Carbonyl reductase 1
  • ER stress
  • Free radicals
  • Lipid peroxidation
  • Lipogenesis
  • Pancreatic β-cell failure
  • Reactive oxygen species
  • Type 2 diabetes

Fingerprint Dive into the research topics of 'Carbonyl reductase 1 protects pancreatic β-cells against oxidative stress-induced apoptosis in glucotoxicity and glucolipotoxicity'. Together they form a unique fingerprint.

Cite this