Antioxidant and regulatory role of mitochondrial uncoupling protein UCP2 in pancreatic beta-cells
Language English Country Czech Republic Media print
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
24564667
DOI
10.33549/physiolres.932633
PII: 932633
Knihovny.cz E-resources
- MeSH
- Antioxidants metabolism MeSH
- Insulin-Secreting Cells metabolism MeSH
- Glucose metabolism MeSH
- Insulin biosynthesis MeSH
- Ion Channels metabolism MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Mitochondrial Proteins metabolism MeSH
- Mitochondria metabolism MeSH
- Oxidation-Reduction MeSH
- Oxidative Stress physiology MeSH
- Reactive Oxygen Species metabolism MeSH
- Gene Expression Regulation physiology MeSH
- Uncoupling Protein 2 MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Antioxidants MeSH
- Glucose MeSH
- Insulin MeSH
- Ion Channels MeSH
- Mitochondrial Proteins MeSH
- Reactive Oxygen Species MeSH
- UCP2 protein, human MeSH Browser
- Uncoupling Protein 2 MeSH
Research on brown adipose tissue and its hallmark protein, mitochondrial uncoupling protein UCP1, has been conducted for half a century and has been traditionally studied in the Institute of Physiology (AS CR, Prague), likewise UCP2 residing in multiple tissues for the last two decades. Our group has significantly contributed to the elucidation of UCP uncoupling mechanism, fully dependent on free fatty acids (FFAs) within the inner mitochondrial membrane. Now we review UCP2 physiological roles emphasizing its roles in pancreatic beta-cells, such as antioxidant role, possible tuning of redox homeostasis (consequently UCP2 participation in redox regulations), and fine regulation of glucose-stimulated insulin secretion (GSIS). For example, NADPH has been firmly established as being a modulator of GSIS and since UCP2 may influence redox homeostasis, it likely affects NADPH levels. We also point out the role of phospholipase iPLA2 isoform gamma in providing FFAs for the UCP2 antioxidant function. Such initiation of mild uncoupling hypothetically precedes lipotoxicity in pancreatic beta-cells until it reaches the pathological threshold, after which the antioxidant role of UCP2 can be no more cell-protective, for example due to oxidative stress-accumulated mutations in mtDNA. These mechanisms, together with impaired autocrine insulin function belong to important causes of Type 2 diabetes etiology.
Physiol Res. 2015;64(2):277 PubMed
References provided by Crossref.org
Mitochondrial Physiology of Cellular Redox Regulations
Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity
