| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print August 23, 2001
J. Biol. Chem, 10.1074/jbc.C100160200
Submitted on April 3, 2001
Revised on August 14, 2001
Accepted on August 22, 2001
Department of Internal Medicine, University of Tokyo, Tokyo 113-8655
Corresponding Author: tobe-tky{at}umin.ac.jp
We previously demonstrated that insulin receptor substrate (IRS)-2-/- mice develop diabetes due to insulin resistance in the liver and failure to undergo b-cell hyperplasia.Å@To understand the role of the liver in the development of diabetes in IRS-2-/- mice, we performed a global gene expression study by murine 11K oligonucleotide microarray (Affymetrix) using liver samples. Quite unexpectedly, remarkable induction of the sterol regulatory element-binding protein (SREBP)-1 gene, a downstream target of insulin, was detected in 16-week-old IRS-2-/- mouse liver, where insulin-mediated intracellular signaling events, including PI3-kinase activation, were substantially attenuated. Expression of SREBP-1 downstream genes, such as the spot 14, ATP citrate-lyase, fatty acid synthase, and malic enzyme genes, was also increased. RNase protection assay revealed that expression of SREBP-1c, but not SREBP-1a, was increased. All these findings were confirmed by Northern blot analysis. Liver triglyceride content was significantly increased in IRS-2-/- mice, assuring the physiological importance of SREBP-1 gene induction. SREBP-1 gene up-regulation was detectable even in 6-week-old euglycemic IRS-2-/- mouse liver. These young mice showed increased adiposity associated with hyperleptinemia. In addition, low-dose leptin administration, enough to reduce food intake and body weight in wild-type mice, failed to do so in IRS-2-/- mice, suggesting that IRS-2-/- mice had leptin resistance. Interestingly, high-dose leptin administration reduced SREBP-1 expression in IRS-2-/- mouse liver. Thus, IRS-2 gene disruption results in leptin resistance, causing a SREBP-1 gene induction, obesity, fatty liver, and diabetes.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Erhuma, A. M. Salter, D. V. Sculley, S. C. Langley-Evans, and A. J. Bennett Prenatal exposure to a low-protein diet programs disordered regulation of lipid metabolism in the aging rat Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1702 - E1714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kamei, K. Tobe, R. Suzuki, M. Ohsugi, T. Watanabe, N. Kubota, N. Ohtsuka-Kowatari, K. Kumagai, K. Sakamoto, M. Kobayashi, et al. Overexpression of Monocyte Chemoattractant Protein-1 in Adipose Tissues Causes Macrophage Recruitment and Insulin Resistance J. Biol. Chem., September 8, 2006; 281(36): 26602 - 26614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Biddinger, M. Miyazaki, J. Boucher, J. M. Ntambi, and C. R. Kahn Leptin Suppresses Stearoyl-CoA Desaturase 1 by Mechanisms Independent of Insulin and Sterol Regulatory Element-Binding Protein-1c. Diabetes, July 1, 2006; 55(7): 2032 - 2041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wang, G. Kouri, and C. B. Wollheim ER stress and SREBP-1 activation are implicated in {beta}-cell glucolipotoxicity J. Cell Sci., September 1, 2005; 118(17): 3905 - 3915. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Jiang, S. E. Liebman, M. S. Lucia, C. L. Phillips, and M. Levi Calorie Restriction Modulates Renal Expression of Sterol Regulatory Element Binding Proteins, Lipid Accumulation, and Age-Related Renal Disease J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2385 - 2394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-S. Im, S.-Y. Kang, S.-Y. Kim, H.-i. Kim, J.-W. Kim, K.-S. Kim, and Y.-H. Ahn Glucose-Stimulated Upregulation of GLUT2 Gene Is Mediated by Sterol Response Element-Binding Protein-1c in the Hepatocytes Diabetes, June 1, 2005; 54(6): 1684 - 1691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Suzuki, K. Tobe, M. Aoyama, K. Sakamoto, M. Ohsugi, N. Kamei, S. Nemoto, A. Inoue, Y. Ito, S. Uchida, et al. Expression of DGAT2 in White Adipose Tissue Is Regulated by Central Leptin Action J. Biol. Chem., February 4, 2005; 280(5): 3331 - 3337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A M Diehl, Z P Li, H Z Lin, and S Q Yang Cytokines and the pathogenesis of non-alcoholic steatohepatitis Gut, February 1, 2005; 54(2): 303 - 306. [Full Text] [PDF]
|
|
|
|
|
|
Y. Terauchi, J. Matsui, J. Kamon, T. Yamauchi, N. Kubota, K. Komeda, S. Aizawa, Y. Akanuma, M. Tomita, and T. Kadowaki Increased Serum Leptin Protects From Adiposity Despite the Increased Glucose Uptake in White Adipose Tissue in Mice Lacking p85{alpha} Phosphoinositide 3-Kinase Diabetes, September 1, 2004; 53(9): 2261 - 2270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Suzuki, K. Tobe, M. Aoyama, A. Inoue, K. Sakamoto, T. Yamauchi, J. Kamon, N. Kubota, Y. Terauchi, H. Yoshimatsu, et al. Both Insulin Signaling Defects in the Liver and Obesity Contribute to Insulin Resistance and Cause Diabetes in Irs2-/- Mice J. Biol. Chem., June 11, 2004; 279(24): 25039 - 25049. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ahluwalia, K. H. Clodfelter, and D. J. Waxman Sexual Dimorphism of Rat Liver Gene Expression: Regulatory Role of Growth Hormone Revealed by Deoxyribonucleic Acid Microarray Analysis Mol. Endocrinol., March 1, 2004; 18(3): 747 - 760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsuzaka, H. Shimano, N. Yahagi, M. Amemiya-Kudo, H. Okazaki, Y. Tamura, Y. Iizuka, K. Ohashi, S. Tomita, M. Sekiya, et al. Insulin-Independent Induction of Sterol Regulatory Element-Binding Protein-1c Expression in the Livers of Streptozotocin-Treated Mice Diabetes, March 1, 2004; 53(3): 560 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Shimizu, S. Ugi, H. Maegawa, K. Egawa, Y. Nishio, T. Yoshizaki, K. Shi, Y. Nagai, K. Morino, K.-i. Nemoto, et al. Protein-tyrosine Phosphatase 1B as New Activator for Hepatic Lipogenesis via Sterol Regulatory Element-binding Protein-1 Gene Expression J. Biol. Chem., October 31, 2003; 278(44): 43095 - 43101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, P. Maechler, P. A. Antinozzi, L. Herrero, K. A. Hagenfeldt-Johansson, A. Bjorklund, and C. B. Wollheim The Transcription Factor SREBP-1c Is Instrumental in the Development of beta -Cell Dysfunction J. Biol. Chem., May 2, 2003; 278(19): 16622 - 16629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Akune, N. Ogata, K. Hoshi, N. Kubota, Y. Terauchi, K. Tobe, H. Takagi, Y. Azuma, T. Kadowaki, K. Nakamura, et al. Insulin receptor substrate-2 maintains predominance of anabolic function over catabolic function of osteoblasts J. Cell Biol., October 14, 2002; 159(1): 147 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Rondinone, J. M. Trevillyan, J. Clampit, R. J. Gum, C. Berg, P. Kroeger, L. Frost, B. A. Zinker, R. Reilly, R. Ulrich, et al. Protein Tyrosine Phosphatase 1B Reduction Regulates Adiposity and Expression of Genes Involved in Lipogenesis Diabetes, August 1, 2002; 51(8): 2405 - 2411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Scearce, J. E. Brestelli, S. K. McWeeney, C. S. Lee, J. Mazzarelli, D. F. Pinney, A. Pizarro, C. J. Stoeckert Jr., S. W. Clifton, M. A. Permutt, et al. Functional Genomics of the Endocrine Pancreas: The Pancreas Clone Set and PancChip, New Resources for Diabetes Research Diabetes, July 1, 2002; 51(7): 1997 - 2004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sun, S. Liu, S. Ferguson, L. Wang, P. Klepcyk, J. S. Yun, and J. E. Friedman Phosphoenolpyruvate Carboxykinase Overexpression Selectively Attenuates Insulin Signaling and Hepatic Insulin Sensitivity in Transgenic Mice J. Biol. Chem., June 21, 2002; 277(26): 23301 - 23307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Soulet and S. Rivest Perspective: How to Make Microarray, Serial Analysis of Gene Expression, and Proteomic Relevant to Day-to-Day Endocrine Problems and Physiological Systems Endocrinology, June 1, 2002; 143(6): 1995 - 2001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Scearce, J. E. Brestelli, S. K. McWeeney, C. S. Lee, J. Mazzarelli, D. F. Pinney, A. Pizarro, C. J. Stoeckert Jr., S. W. Clifton, M. A. Permutt, et al. Functional Genomics of the Endocrine Pancreas: The Pancreas Clone Set and PancChip, New Resources for Diabetes Research Diabetes, July 1, 2002; 51(7): 1997 - 2004. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
