Am J Physiol Cell Physiol Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 285: C222-C235, 2003. First published March 26, 2003; doi:10.1152/ajpcell.00006.2003
0363-6143/03 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
285/1/C222    most recent
00006.2003v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (65)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cohen, A. W.
Right arrow Articles by Lisanti, M. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cohen, A. W.
Right arrow Articles by Lisanti, M. P.

CELLULAR METABOLISM

Caveolin-1-deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissue

Alex W. Cohen,1,2 Babak Razani,1,2 Xiao Bo Wang,1,2 Terry P. Combs,3 Terence M. Williams,1,2 Philipp E. Scherer,3 and Michael P. Lisanti1,2

1Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx; 2Division of Hormone-dependent Tumor Biology, The Albert Einstein Cancer Center, Bronx; 3Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461

Submitted 7 January 2003 ; accepted in final form 19 March 2003

Several lines of evidence suggest that a functional relationship exists between caveolin-1 and insulin signaling. However, it remains unknown whether caveolin-1 is normally required for proper insulin receptor signaling in vivo. To address this issue, we examined the status of insulin receptor signaling in caveolin-1 (–/–)-deficient (Cav-1 null) mice. Here, we show that Cav-1 null mice placed on a high-fat diet for 9 mo develop postprandial hyperinsulinemia. An insulin tolerance test (ITT) revealed that young Cav-1 null mice on a normal chow diet are significantly unresponsive to insulin, compared with their wild-type counterparts. This insulin resistance is due to a primary defect in adipose tissue, as evidenced by drastically reduced insulin receptor protein levels (>90%), without any changes in insulin receptor mRNA levels. These data suggest that caveolin-1 acts as a molecular chaperone that is necessary for the proper stabilization of the insulin receptor in adipocytes in vivo. In support of this notion, we demonstrate that recombinant expression of caveolin-1 in Cav-1 null mouse embryo fibroblasts rescues insulin receptor protein expression. These data provide evidence that the lean body phenotype observed in the Cav-1 knockout mice is due, at least in part, to a defect in insulin-regulated lipogenesis.

caveolae; caveolin; insulin signaling; protein stabilization; knockout mice


Address for reprint requests and other correspondence: M. P. Lisanti, Dept. of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461 (E-mail: lisanti{at}aecom.yu.edu).




This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
M. L. Styers, A. K. O'Connor, R. Grabski, E. Cormet-Boyaka, and E. Sztul
Depletion of {beta}-COP reveals a role for COP-I in compartmentalization of secretory compartments and in biosynthetic transport of caveolin-1
Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1485 - C1498.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. W. Ryter and A. M. K. Choi
Caveolin-1: a critical regulator of pulmonary vascular architecture and nitric oxide bioavailability in pulmonary hypertension
Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L862 - L864.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. A. Predescu, D. N. Predescu, and A. B. Malik
Molecular determinants of endothelial transcytosis and their role in endothelial permeability
Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L823 - L842.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
N. Yang, C. Ying, M. Xu, X. Zuo, X. Ye, L. Liu, Y. Nara, and X. Sun
High-fat diet up-regulates caveolin-1 expression in aorta of diet-induced obese but not in diet-resistant rats
Cardiovasc Res, October 1, 2007; 76(1): 167 - 174.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
M. Inoue, S.-H. Chiang, L. Chang, X.-W. Chen, and A. R. Saltiel
Compartmentalization of the Exocyst Complex in Lipid Rafts Controls Glut4 Vesicle Tethering
Mol. Biol. Cell, May 1, 2006; 17(5): 2303 - 2311.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
C. Schwencke, R. C. Braun-Dullaeus, C. Wunderlich, and R. H. Strasser
Caveolae and caveolin in transmembrane signaling: Implications for human disease
Cardiovasc Res, April 1, 2006; 70(1): 42 - 49.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
K. Miyawaki-Shimizu, D. Predescu, J. Shimizu, M. Broman, S. Predescu, and A. B. Malik
siRNA-induced caveolin-1 knockdown in mice increases lung vascular permeability via the junctional pathway
Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L405 - L413.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
F. Capozza, T. P. Combs, A. W. Cohen, Y.-R. Cho, S.-Y. Park, W. Schubert, T. M. Williams, D. L. Brasaemle, L. A. Jelicks, P. E. Scherer, et al.
Caveolin-3 knockout mice show increased adiposity and whole body insulin resistance, with ligand-induced insulin receptor instability in skeletal muscle
Am J Physiol Cell Physiol, June 1, 2005; 288(6): C1317 - C1331.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. W. Cohen, W. Schubert, D. L. Brasaemle, P. E. Scherer, and M. P. Lisanti
Caveolin-1 Expression Is Essential for Proper Nonshivering Thermogenesis in Brown Adipose Tissue
Diabetes, March 1, 2005; 54(3): 679 - 686.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. M. Bauer, J. Yu, Y. Chen, R. Hickey, P. N. Bernatchez, R. Looft-Wilson, Y. Huang, F. Giordano, R. V. Stan, and W. C. Sessa
Endothelial-specific expression of caveolin-1 impairs microvascular permeability and angiogenesis
PNAS, January 4, 2005; 102(1): 204 - 209.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
K. Kabayama, T. Sato, F. Kitamura, S. Uemura, B. W. Kang, Y. Igarashi, and J.-i. Inokuchi
TNF{alpha}-induced insulin resistance in adipocytes as a membrane microdomain disorder: involvement of ganglioside GM3
Glycobiology, January 1, 2005; 15(1): 21 - 29.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
A. W. Cohen, R. Hnasko, W. Schubert, and M. P. Lisanti
Role of Caveolae and Caveolins in Health and Disease
Physiol Rev, October 1, 2004; 84(4): 1341 - 1379.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. W. Cohen, B. Razani, W. Schubert, T. M. Williams, X. B. Wang, P. Iyengar, D. L. Brasaemle, P. E. Scherer, and M. P. Lisanti
Role of Caveolin-1 in the Modulation of Lipolysis and Lipid Droplet Formation
Diabetes, May 1, 2004; 53(5): 1261 - 1270.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
W. C. Sessa
Atheroprotection in the Absence of "Caves": Is it the Fat, the Vessels, or Both?
Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 4 - 6.
[Full Text] [PDF]

Home page
 Mol. Interv.Home page
R. Hnasko and M. P. Lisanti
The Biology of Caveolae: Lessons from Caveolin Knockout Mice and Implications for Human Disease
Mol. Interv., December 1, 2003; 3(8): 445 - 464.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. W. Cohen, T. P. Combs, P. E. Scherer, and M. P. Lisanti
Role of caveolin and caveolae in insulin signaling and diabetes
Am J Physiol Endocrinol Metab, December 1, 2003; 285(6): E1151 - E1160.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2003 by the American Physiological Society.