Document Detail

Role of metabolically generated reactive oxygen species for lipotoxicity in pancreatic β-cells.
MedLine Citation:
PMID:  21029312     Owner:  NLM     Status:  MEDLINE    
Chronically elevated concentrations of non-esterified fatty acids (NEFAs) in type 2 diabetes may be involved in β-cell dysfunction and apoptosis. It has been shown that long-chain saturated NEFAs exhibit a strong cytotoxic effect upon insulin-producing cells, while short-chain as well as unsaturated NEFAs are well tolerated. Moreover, long-chain unsaturated NEFAs counteract the toxicity of palmitic acid. Reactive oxygen species (ROS) formation and gene expression analyses together with viability assays in different β-cell lines showed that the G-protein-coupled receptors 40 and 120 do not mediate lipotoxicity. This is independent from the role, which these receptors, specifically GPR40, play in the potentiation of glucose-induced insulin secretion by saturated and unsaturated long-chain NEFAs. Long-chain NEFAs are not only metabolized in the mitochondria but also in peroxisomes. In contrast to mitochondrial β-oxidation, the acyl-coenzyme A (CoA) oxidases in the peroxisomes form hydrogen peroxide and not reducing equivalents. As β-cells almost completely lack catalase, they are exceptionally vulnerable to hydrogen peroxide generated in peroxisomes. ROS generation in the respiratory chain is less important because overexpression of catalase and superoxide dismutase in the mitochondria do not provide protection. Thus, peroxisomally generated hydrogen peroxide is the likely ROS that causes pancreatic β-cell dysfunction and ultimately β-cell death.
W Gehrmann; M Elsner; S Lenzen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Diabetes, obesity & metabolism     Volume:  12 Suppl 2     ISSN:  1463-1326     ISO Abbreviation:  Diabetes Obes Metab     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-29     Completed Date:  2011-03-09     Revised Date:  2011-11-03    
Medline Journal Info:
Nlm Unique ID:  100883645     Medline TA:  Diabetes Obes Metab     Country:  England    
Other Details:
Languages:  eng     Pagination:  149-58     Citation Subset:  IM    
Copyright Information:
© 2010 Blackwell Publishing Ltd.
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Apoptosis / drug effects
Fatty Acids, Nonesterified / pharmacology
Gene Expression Regulation
Hydrogen Peroxide / pharmacology
Insulin / pharmacology
Insulin-Secreting Cells / cytology,  metabolism*
Mitochondria / drug effects,  metabolism*
Oxidation-Reduction / drug effects
Reactive Oxygen Species / metabolism*
Receptors, G-Protein-Coupled / physiology
Reg. No./Substance:
0/FFAR1 protein, human; 0/Fatty Acids, Nonesterified; 0/O3FAR1 protein, human; 0/Reactive Oxygen Species; 0/Receptors, G-Protein-Coupled; 11061-68-0/Insulin; 7722-84-1/Hydrogen Peroxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Reactive oxygen species and uncoupling protein 2 in pancreatic ?-cell function.
Next Document:  The hypoxia response pathway and ?-cell function.