Journal article
Nfe2l1 deficiency mitigates streptozotocin-induced pancreatic β-cell destruction and development of diabetes in male mice
Food and chemical toxicology, Vol.158, pp.112633-112633
12/2021
DOI: 10.1016/j.fct.2021.112633
PMID: 34699923
Abstract
Streptozotocin (STZ) is a pancreatic β cell-specific toxicant that is widely used to generate models of diabetes in rodents as well as in the treatment of tumors derived from pancreatic β cells. DNA alkylation, oxidative stress and mitochondrial toxicity have been recognized as the mechanisms for STZ-induced pancreatic β cell damage. Here, we found that pancreatic β cell-specific deficiency of nuclear factor erythroid-derived factor 2-related factor 1 (NFE2L1), a master regulator of the cellular adaptive response to a variety of stresses, in mice led to a dramatic resistance to STZ-induced hyperglycemia. Indeed, fifteen days subsequent to last dosage of STZ, the pancreatic β cell specific Nfe2l1 knockout [Nfe2l1(β)-KO] mice showed reduced hyperglycemia, improved glucose tolerance, higher plasma insulin and more intact islets surrounded by exocrine acini compared to the Nfe2l1-Flox control mice with the same treatment. Immunohistochemistry staining revealed a greater amount of insulin-positive cells in the pancreas of Nfe2l1(β)-KO mice than those in Nfe2l1-Flox mice 15 days after the last STZ injection. In line with this observation, both isolated Nfe2l1(β)-KO islets and Nfe2l1-deficient MIN6 (Nfe2l1-KD) cells were resistant to STZ-induced toxicity and apoptosis. Furthermore, pretreatment of the MIN6 cells with glycolysis inhibitor 2-Deoxyglucose sensitized Nfe2l1-KD cells to STZ-induced toxicity. These findings demonstrated that loss of Nfe2l1 attenuates pancreatic β cells damage and dysfunction caused by STZ exposure, partially due to Nfe2l1 deficiency-induced metabolic switch to enhanced glycolysis.
Details
- Title: Subtitle
- Nfe2l1 deficiency mitigates streptozotocin-induced pancreatic β-cell destruction and development of diabetes in male mice
- Creators
- Simeng Bao - Program of Environmental Toxicology, School of Public Health, China Medical University No 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, PR China.Hongzhi Zheng - China Medical UniversityChengjie Chen - Program of Environmental Toxicology, School of Public Health, China Medical University No 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, PR China.Yuhang Zhang - Program of Environmental Toxicology, School of Public Health, China Medical University No 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, PR China.Lina Bao - Program of Environmental Toxicology, School of Public Health, China Medical University No 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, PR China.Bei Yang - Department of Histology and Embryology, School of Basic Medical Sciences, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China.Yongyong Hou - Program of Environmental Toxicology, School of Public Health, China Medical University No 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, PR China.Yanyan Chen - China Medical UniversityQiang Zhang - Emory UniversityJingbo Pi - Program of Environmental Toxicology, School of Public Health, China Medical University No 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, PR China.Jingqi Fu - Program of Environmental Toxicology, School of Public Health, China Medical University No 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, PR China.
- Resource Type
- Journal article
- Publication Details
- Food and chemical toxicology, Vol.158, pp.112633-112633
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.fct.2021.112633
- PMID
- 34699923
- ISSN
- 0278-6915
- eISSN
- 1873-6351
- Language
- English
- Date published
- 12/2021
- Academic Unit
- Neurology
- Record Identifier
- 9984302209102771
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