scholarly journals Antioxidant and Regulatory Role of Mitochondrial Uncoupling Protein UCP2 in Pancreatic β-cells

2014 ◽  
pp. S73-S91 ◽  
Author(s):  
P. JEŽEK ◽  
T. OLEJÁR ◽  
K. SMOLKOVÁ ◽  
J. JEŽEK ◽  
A. DLASKOVÁ ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Redox Homeostasis ◽  
Inner Mitochondrial Membrane ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose ◽  
Glucose Stimulated Insulin Secretion

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 β-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  in providing FFAs for the UCP2 antioxidant function. Such initiation of mild uncoupling hypothetically precedes lipotoxicity in pancreatic β-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.

scholarly journals Neuroprotective Role of Mitochondrial Uncoupling Protein 2 in Cerebral Stroke

2009 ◽  
Vol 29 (6) ◽  
pp. 1069-1078 ◽  
Author(s):  
Suresh L Mehta ◽  
P. Andy Li
Keyword(s):  
Uncoupling Protein ◽  
Cellular Damage ◽  
Cerebral Stroke ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Uncoupling ◽  
Mitochondria Membrane Potential ◽  
Mitochondrial Uncoupling Protein ◽  
Mitochondrial Transporter ◽  
Develop Strategy

The uncoupling proteins (UCPs) are mitochondrial transporter proteins involved in proton conductance across inner mitochondrial membrane (IMM). UCP2, which is one of the members of this class of proteins, has a wide but restricted tissue distribution including brain. Its physiologic role according to emerging evidences, although still not clear, indicate that distribution of UCP2 may be related to regulation of mitochondria membrane potential (ΔΨm), production of reactive oxygen species (ROS), preservation of calcium homeostasis, modulation of neuronal activity, and eventually inhibition of cellular damage. These factors are very important in determining the fate of neurons and damage progression in the brain during various neurodegenerative diseases including cerebral stroke. Recent evidence indicates that an increased expression and activity of UCP2 are well correlated with neuronal survival after stroke and trauma. This review briefly covers the present understanding of UCP2, which eventually may be beneficial to understand the precise role of UCP2 to develop strategy to identify its potential therapeutic application.

scholarly journals Mitochondrial uncoupling protein 2 in pancreatic β-cells

2010 ◽  
Vol 12 ◽  
pp. 134-140 ◽  
Author(s):  
M. D. Brand ◽  
N. Parker ◽  
C. Affourtit ◽  
S. A. Mookerjee ◽  
V. Azzu
Keyword(s):  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein

3,5,3′-Triiodothyronine actively stimulates UCP in brown fat under minimal sympathetic activity

1999 ◽  
Vol 276 (1) ◽  
pp. E179-E187 ◽  
Author(s):  
Marcelo Branco ◽  
Miriam Ribeiro ◽  
Nubio Negrão ◽  
Antonio C. Bianco
Keyword(s):  
Uncoupling Protein ◽  
Thermal Response ◽  
Male Rats ◽  
Intact Male ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Norepinephrine Infusion ◽  
Brown Adipose ◽  
Intact Rats

To investigate the role of type II 5′-deiodinase (5′D-II) in the expression of mitochondrial uncoupling protein (UCP) in brown adipose tissue (BAT), we injected intact male rats with reverse (r) 3,5,3′-triiodothyronine (T3; 100 μg ⋅ 100 g body wt−1 ⋅ day−1), an inhibitor of 5′D-II, for 2–5 days. UCP decreased by ∼20% in rats kept at 28°C and failed to increase during cold exposure (4°C). Next, thyroxine treatment (1–10 μg ⋅ 100 g body wt−1 ⋅ day−1) increased nuclear T3 in rats kept at 28 or 4°C. In these rats, nuclear T3 correlated positively with UCP. In addition, T3 (1–50 μg ⋅ 100 g body wt−1 ⋅ day−1) given to intact rats (5–15 days; 28°C) induced an approximately twofold increase in UCP. In these T3-treated animals, the interscapular BAT thermal response to norepinephrine infusion also correlated positively with T3 dose and UCP content. Treatment with propranolol or reserpine failed to block the T3 induction of UCP (∼1.8- and ∼2.3-fold). The results emphasize the importance of local 5′D-II and reveal an independent role of T3 in the expression of UCP.

scholarly journals Peroxisome Proliferator-Activated Receptor α (PPARα) Potentiates, whereas PPARγ Attenuates, Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3266-3276 ◽  
Author(s):  
Kim Ravnskjaer ◽  
Michael Boergesen ◽  
Blanca Rubi ◽  
Jan K. Larsen ◽  
Tina Nielsen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Mitochondrial Membrane ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Stimulated Insulin Secretion

Abstract Fatty acids (FAs) are known to be important regulators of insulin secretion from pancreatic β-cells. FA-coenzyme A esters have been shown to directly stimulate the secretion process, whereas long-term exposure of β-cells to FAs compromises glucose-stimulated insulin secretion (GSIS) by mechanisms unknown to date. It has been speculated that some of these long-term effects are mediated by members of the peroxisome proliferator-activated receptor (PPAR) family via an induction of uncoupling protein-2 (UCP2). In this study we show that adenoviral coexpression of PPARα and retinoid X receptor α (RXRα) in INS-1E β-cells synergistically and in a dose- and ligand-dependent manner increases the expression of known PPARα target genes and enhances FA uptake and β-oxidation. In contrast, ectopic expression of PPARγ/RXRα increases FA uptake and deposition as triacylglycerides. Although the expression of PPARα/RXRα leads to the induction of UCP2 mRNA and protein, this is not accompanied by reduced hyperpolarization of the mitochondrial membrane, indicating that under these conditions, increased UCP2 expression is insufficient for dissipation of the mitochondrial proton gradient. Importantly, whereas expression of PPARγ/RXRα attenuates GSIS, the expression of PPARα/RXRα potentiates GSIS in rat islets and INS-1E cells without affecting the mitochondrial membrane potential. These results show a strong subtype specificity of the two PPAR subtypes α and γ on lipid partitioning and insulin secretion when systematically compared in a β-cell context.

Effects of intravenous isoproterenol (β-agonist) administration on expression and synthesis of ovine uncoupling protein-1

1999 ◽  
Vol 1999 ◽  
pp. 164-164
Author(s):  
D.S. Finn ◽  
P. Trayhurn ◽  
J. Struthers ◽  
M.A. Lomax
Keyword(s):  
Adipose Tissue ◽  
Cold Stress ◽  
Uncoupling Protein ◽  
Uncoupling Protein 1 ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Neonatal Life ◽  
Adrenoceptor Agonist ◽  
Brown Adipose

A crucial factor in the prevention of hypothermia in the neonatal lamb is the functional activitation of a mitochondrial uncoupling protein (UCP1) in brown adipose tissue. UCP1 disappears from lamb brown fat over the first 14 days of life (Finn et al., 1998), but it is not known whether this process can be modulated in lambs by the release of catecholamines which have been established in rodents as a mediator of the response to cold stress. This study examines the effect of administering a β-adrenoceptor agonist on the disappearance of UCP1 and UCP1 mRNA during early neonatal life, using immunohistochemistry and in situ hybridization.

Thyroxine 5'-deiodinase in brown adipose tissue of myopathic hamsters

1986 ◽  
Vol 251 (1) ◽  
pp. E8-E13 ◽  
Author(s):  
J. Kopecky ◽  
L. Sigurdson ◽  
I. R. Park ◽  
J. Himms-Hagen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Fat Diet ◽  
Uncoupling Protein ◽  
High Fat ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Endogenous Production ◽  
Deiodinase Activity ◽  
Brown Adipose

Myopathic Syrian hamsters (BIO 14.6) have less brown adipose tissue (BAT) than normal. The trophic response of this tissue to cold is smaller than normal and trophic responses to diet and to photoperiod are absent. The objective was to find out whether activity of thyroxine 5'-deiodinase in their BAT was increased normally in response to cold and thus whether a defect in endogenous production of 3,5,3'-triiodothyronine might underlie the attenuated trophic response. The effect of feeding a high-fat diet on activity of 5'-deiodinase was also studied. Cold acclimation increased thyroxine 5'-deiodinase activity in BAT of the myopathic hamster, but the total remained smaller than normal because of the smaller size. The cold-induced increase in concentration of mitochondrial uncoupling protein was also smaller than normal. The level of serum 3,5,3'-triiodothyronine was low in myopathic hamsters and remained lower than normal when they were cold-exposed or cold acclimated. Feeding the high-fat diet to myopathic hamsters resulted in a greater than normal suppression of thyroxine 5'-deiodinase activity than in normal hamsters; the normal increases in protein content and in concentration of mitochondrial uncoupling protein were absent. We conclude that the defective trophic response of BAT of the myopathic hamster is not secondary to defective regulation of its thyroxine 5'-deiodinase activity because this activity does not appear to be obligatorily linked to hypertrophy of BAT. The low level of serum 3,5,3'-triiodothyronine in the myopathic hamster may be secondary to reduced capacity for peripheral thyroxine deiodination in its BAT.

scholarly journals Identification of a Functioning Mitochondrial Uncoupling Protein 1 in Thymus

2005 ◽  
Vol 280 (16) ◽  
pp. 15534-15543 ◽  
Author(s):  
Audrey M. Carroll ◽  
Lee R. Haines ◽  
Terry W. Pearson ◽  
Padraic G. Fallon ◽  
Caitríona M. Walsh ◽  
...  
Keyword(s):  
Metabolic Flux ◽  
Uncoupling Protein ◽  
Mitochondrial Uncoupling ◽  
Knock Out ◽  
Mitochondrial Uncoupling Protein ◽  
Rna Transcripts ◽  
Peptide Mass ◽  
Brown Adipose ◽  
Knock Out Mice ◽  
Kinetics Of

We present evidence that rat and mouse thymi contain mitochondrial uncoupling protein (UCP 1). Reverse transcriptase-PCR detected RNA transcripts for UCP 1 in whole thymus and in thymocytes. Furthermore, using antibodies to UCP 1 the protein was also detected in mitochondria isolated from whole thymus and thymocytes but not in thymus mitochondria from UCP 1 knock-out mice. Evidence for functional UCP 1 in thymus mitochondria was obtained by a comparative analysis with the kinetics of GDP binding in mitochondria from brown adipose tissue. Both tissues showed equivalentBmaxandKDvalues. In addition, a large component of the nonphosphorylating oxygen consumption by thymus mitochondria was inhibited by GDP and subsequently stimulated by addition of nanomolar concentrations of palmitate. UCP 1 was purified from thymus mitochondria by hydroxyapatite chromatography. The isolated protein was identified by peptide mass mapping and tandem mass spectrometry by using MALDI-TOF and LC-MS/MS, respectively. We conclude that the thymus contains a functioning UCP 1 that has the capacity to regulate metabolic flux and production of reactive oxygen-containing molecules in the thymus.

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