|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 16, 12520-12529, April 20, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the UCP3 is a mitochondrial membrane protein
expressed in humans selectively in skeletal muscle. To determine the
mechanisms by which UCP3 plays a role in regulating glucose metabolism,
we expressed human UCP3 in L6 myotubes by
adenovirus-mediated gene transfer and in H9C2
cardiomyoblasts by stable transfection with a tetracycline-repressible UCP3 construct. Expression of UCP3 in L6
myotubes increased 2-deoxyglucose uptake 2-fold and cell surface GLUT4
2.3-fold, thereby reaching maximally insulin-stimulated levels in
control myotubes. Wortmannin, LY 294002, or the tyrosine kinase
inhibitor genistein abolished the effect of UCP3 on glucose
uptake, and wortmannin inhibited UCP3-induced GLUT4 cell surface
recruitment. UCP3 overexpression increased phosphotyrosine-associated
phosphoinositide 3-kinase (PI3K) activity 2.2-fold compared with
control cells (p < 0.05). UCP3 overexpression
increased lactate release 1.5- to 2-fold above control cells,
indicating increased glucose metabolism. In
H9C2 cardiomyoblasts stably transfected with
UCP3 under control of a tetracycline-repressible promotor,
removal of doxycycline resulted in detectable levels of UCP3 at 12 h and 2.2-fold induction at 7 days compared with 12 h. In
parallel, glucose transport increased 1.3- and 2-fold at 12 h and
7 days, respectively, and the stimulation was inhibited by wortmannin
or genistein. p85 association with membranes was increased 5.5-fold and
phosphotyrosine-associated PI3K activity 3.8-fold. In contrast,
overexpression of UCP3 in 3T3-L1 adipocytes did not alter
glucose uptake, suggesting tissue-specific effects of human UCP3. Thus,
UCP3 stimulates glucose transport and GLUT4 translocation to the cell
surface in cardiac and skeletal muscle cells by activating a PI3K
dependent pathway.
Uncoupling Protein 3 (UCP3) Stimulates Glucose Uptake in Muscle
Cells through a Phosphoinositide 3-Kinase-dependent
Mechanism*
§¶,§,,,,
,,, and**
Diabetes Unit, Department of Medicine,
Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical
Center and Harvard Medical School, Boston, Massachusetts 02215 and the
Endocrine Research Division, Lilly Research Laboratories, Eli
Lilly and Company, Indianapolis, Indiana 46285
*
This study was supported by National Institutes of Health
Grants DK 43051 (to B. B. K.) and DK 49569 (to B. B. L.) and a
grant from Eli Lilly.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. S Wyrwoll, P. J Mark, T. A Mori, and B. J Waddell Developmental programming of adult hyperinsulinemia, increased proinflammatory cytokine production, and altered skeletal muscle expression of SLC2A4 (GLUT4) and uncoupling protein 3 J. Endocrinol., September 1, 2008; 198(3): 571 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Bezaire, E. L. Seifert, and M.-E. Harper Uncoupling protein-3: clues in an ongoing mitochondrial mystery FASEB J, February 1, 2007; 21(2): 312 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. MacLellan, M. F. Gerrits, A. Gowing, P. J.S. Smith, M. B. Wheeler, and M.-E. Harper Physiological Increases in Uncoupling Protein 3 Augment Fatty Acid Oxidation and Decrease Reactive Oxygen Species Production Without Uncoupling Respiration in Muscle Cells Diabetes, August 1, 2005; 54(8): 2343 - 2350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yvan-Charvet, P. Even, M. Bloch-Faure, M. Guerre-Millo, N. Moustaid-Moussa, P. Ferre, and A. Quignard-Boulange Deletion of the Angiotensin Type 2 Receptor (AT2R) Reduces Adipose Cell Size and Protects From Diet-Induced Obesity and Insulin Resistance Diabetes, April 1, 2005; 54(4): 991 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R Steffensen, S. Y. Neo, T. M Stulnig, V. B Vega, S. S Rahman, G. U Schuster, J.-A. Gustafsson, and E. T Liu Genome-wide expression profiling; a panel of mouse tissues discloses novel biological functions of liver X receptors in adrenals J. Mol. Endocrinol., December 1, 2004; 33(3): 609 - 622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. B. Suliman, K. E. Welty-Wolf, M. Carraway, L. Tatro, and C. A. Piantadosi Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis Cardiovasc Res, November 1, 2004; 64(2): 279 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Perdomo, S. R. Commerford, A.-M. T. Richard, S. H. Adams, B. E. Corkey, R. M. O'Doherty, and N. F. Brown Increased {beta}-Oxidation in Muscle Cells Enhances Insulin-stimulated Glucose Metabolism and Protects against Fatty Acid-induced Insulin Resistance Despite Intramyocellular Lipid Accumulation J. Biol. Chem., June 25, 2004; 279(26): 27177 - 27186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-J. Ma, S.-L. Mao, K. L. Taylor, T. Kanjanabuch, Y. Guan, Y. Zhang, N. J. Brown, L. L. Swift, O. P. McGuinness, D. H. Wasserman, et al. Prevention of Obesity and Insulin Resistance in Mice Lacking Plasminogen Activator Inhibitor 1 Diabetes, February 1, 2004; 53(2): 336 - 346. [Abstract] [Full Text]
|
|
|
|
 |
|
 X. Sun, C. Wray, X. Tian, P.-O. Hasselgren, and J. Lu Expression of uncoupling protein 3 is upregulated in skeletal muscle during sepsis Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E512 - E520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Schrauwen and M. Hesselink UCP2 and UCP3 in muscle controlling body metabolism J. Exp. Biol., August 1, 2002; 205(15): 2275 - 2285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Argyropoulos and M.-E. Harper Molecular Biology of Thermoregulation: Invited Review: Uncoupling proteins and thermoregulation J Appl Physiol, May 1, 2002; 92(5): 2187 - 2198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Schrauwen, M. K.C. Hesselink, E. E. Blaak, L. B. Borghouts, G. Schaart, W. H.M. Saris, and H. A. Keizer Uncoupling Protein 3 Content Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes Diabetes, December 1, 2001; 50(12): 2870 - 2873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cadenas, K. S. Echtay, J. A. Harper, M. B. Jekabsons, J. A. Buckingham, E. Grau, A. Abuin, H. Chapman, J. C. Clapham, and M. D. Brand The Basal Proton Conductance of Skeletal Muscle Mitochondria from Transgenic Mice Overexpressing or Lacking Uncoupling Protein-3 J. Biol. Chem., January 18, 2002; 277(4): 2773 - 2778. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |