Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Table 1
Right arrow Erratum (v51,p1652)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Butler, M.
Right arrow Articles by Monia, B. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Butler, M.
Right arrow Articles by Monia, B. P.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Diabetes 51:1028-1034, 2002
© 2002 by the American Diabetes Association, Inc.

Specific Inhibition of PTEN Expression Reverses Hyperglycemia in Diabetic Mice

Madeline Butler, Robert A. McKay, Ian J. Popoff, William A. Gaarde, Donna Witchell, Susan F. Murray, Nicholas M. Dean, Sanjay Bhanot, and Brett P. Monia

From Isis Pharmaceuticals, Carlsbad, California

Signaling through the phosphatidylinositol 3'-kinase (PI3K) pathway is crucial for metabolic responses to insulin, and defects in PI3K signaling have been demonstrated in type 2 diabetes. PTEN (MMAC1) is a lipid/protein phosphatase that can negatively regulate the PI3K pathway by dephosphorylating phosphatidylinositol (3,4,5)-triphosphate, but it is unclear whether PTEN is physiologically relevant to insulin signaling in vivo. We employed an antisense oligonucleotide (ASO) strategy in an effort to specifically inhibit the expression of PTEN. Transfection of cells in culture with ASO targeting PTEN reduced PTEN mRNA and protein levels and increased insulin-stimulated Akt phosphorylation in {alpha}-mouse liver-12 (AML12) cells. Systemic administration of PTEN ASO once a week in mice suppressed PTEN mRNA and protein expression in liver and fat by up to 90 and 75%, respectively, and normalized blood glucose concentrations in db/db and ob/ob mice. Inhibition of PTEN expression also dramatically reduced insulin concentrations in ob/ob mice, improved the performance of db/db mice during insulin tolerance tests, and increased Akt phosphorylation in liver in response to insulin. These results suggest that PTEN plays a significant role in regulating glucose metabolism in vivo by negatively regulating insulin signaling.


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 DiabetesHome page
M. Bell, H. Wang, H. Chen, J. C. McLenithan, D.-W. Gong, R.-Z. Yang, D. Yu, S. K. Fried, M. J. Quon, C. Londos, et al.
Consequences of Lipid Droplet Coat Protein Downregulation in Liver Cells: Abnormal Lipid Droplet Metabolism and Induction of Insulin Resistance
Diabetes, August 1, 2008; 57(8): 2037 - 2045.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
P. Song, Y. Wu, J. Xu, Z. Xie, Y. Dong, M. Zhang, and M.-H. Zou
Reactive Nitrogen Species Induced by Hyperglycemia Suppresses Akt Signaling and Triggers Apoptosis by Upregulating Phosphatase PTEN (Phosphatase and Tensin Homologue Deleted on Chromosome 10) in an LKB1-Dependent Manner
Circulation, October 2, 2007; 116(14): 1585 - 1595.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. P. Ciaraldi, S. E. Nikoulina, R. A. Bandukwala, L. Carter, and R. R. Henry
Role of Glycogen Synthase Kinase-3{alpha} in Insulin Action in Cultured Human Skeletal Muscle Cells
Endocrinology, September 1, 2007; 148(9): 4393 - 4399.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
F. M. Smith, L. J. Holt, A. S. Garfield, M. Charalambous, F. Koumanov, M. Perry, R. Bazzani, S. A. Sheardown, B. D. Hegarty, R. J. Lyons, et al.
Mice with a Disruption of the Imprinted Grb10 Gene Exhibit Altered Body Composition, Glucose Homeostasis, and Insulin Signaling during Postnatal Life
Mol. Cell. Biol., August 15, 2007; 27(16): 5871 - 5886.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. W. Sloop, A. D. Showalter, A. L. Cox, J. X. C. Cao, A. M. Siesky, H. Y. Zhang, A. R. Irizarry, S. F. Murray, S. L. Booten, E. A. Finger, et al.
Specific Reduction of Hepatic Glucose 6-Phosphate Transporter-1 Ameliorates Diabetes while Avoiding Complications of Glycogen Storage Disease
J. Biol. Chem., June 29, 2007; 282(26): 19113 - 19121.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
K. Y. Kim, H. S. Cho, W. H. Jung, S. S. Kim, and H. G. Cheon
Phosphatase and Tensin Homolog Deleted on Chromosome 10 Suppression Is an Important Process in Peroxisome Proliferator-Activated Receptor-{gamma} Signaling in Adipocytes and Myotubes
Mol. Pharmacol., June 1, 2007; 71(6): 1554 - 1562.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. K. Pandey, X. X. Yu, L. M. Watts, M. D. Michael, K. W. Sloop, A. R. Rivard, T. A. Leedom, V. P. Manchem, L. Samadzadeh, R. A. McKay, et al.
Reduction of Low Molecular Weight Protein-tyrosine Phosphatase Expression Improves Hyperglycemia and Insulin Sensitivity in Obese Mice
J. Biol. Chem., May 11, 2007; 282(19): 14291 - 14299.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
X.-H. Yao and B. L. Gregoire Nyomba
Abnormal glucose homeostasis in adult female rat offspring after intrauterine ethanol exposure
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1926 - R1933.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
M. J. Graham, K. M. Lemonidis, C. P. Whipple, A. Subramaniam, B. P. Monia, S. T. Crooke, and R. M. Crooke
Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice
J. Lipid Res., April 1, 2007; 48(4): 763 - 767.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
J. G. Karras, J. R. Crosby, M. Guha, D. Tung, D. A. Miller, W. A. Gaarde, R. S. Geary, B. P. Monia, and S. A. Gregory
Anti-Inflammatory Activity of Inhaled IL-4 Receptor-{alpha} Antisense Oligonucleotide in Mice
Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 276 - 285.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
E. E. Swayze, A. M. Siwkowski, E. V. Wancewicz, M. T. Migawa, T. K. Wyrzykiewicz, G. Hung, B. P. Monia, and a. C. F. Bennett
Antisense oligonucleotides containing locked nucleic acid improve potency but cause significant hepatotoxicity in animals
Nucleic Acids Res., January 28, 2007; 35(2): 687 - 700.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. Xu, L. Gowen, C. Raphalides, K. K. Hoyer, J. G. Weinger, M. Renard, J. J. Troke, B. Vaitheesyaran, W.N. P. Lee, M. F. Saad, et al.
Decreased Hepatic Futile Cycling Compensates for Increased Glucose Disposal in the Pten Heterodeficient Mouse
Diabetes, December 1, 2006; 55(12): 3372 - 3380.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
L. Mahimainathan, F. Das, B. Venkatesan, and G. G. Choudhury
Mesangial Cell Hypertrophy by High Glucose Is Mediated by Downregulation of the Tumor Suppressor PTEN.
Diabetes, July 1, 2006; 55(7): 2115 - 2125.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K.-T. T. Nguyen, P. Tajmir, C. H. Lin, N. Liadis, X.-D. Zhu, M. Eweida, G. Tolasa-Karaman, F. Cai, R. Wang, T. Kitamura, et al.
Essential Role of Pten in Body Size Determination and Pancreatic {beta}-Cell Homeostasis In Vivo
Mol. Cell. Biol., June 15, 2006; 26(12): 4511 - 4518.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
E. Koller, S. Propp, H. Zhang, C. Zhao, X. Xiao, M. Chang, S. A. Hirsch, P. J. Shepard, S. Koo, C. Murphy, et al.
Use of a Chemically Modified Antisense Oligonucleotide Library to Identify and Validate Eg5 (Kinesin-Like 1) as a Target for Antineoplastic Drug Development
Cancer Res., February 15, 2006; 66(4): 2059 - 2066.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. A. Kushner, L. Simpson, L. M. Wartschow, S. Guo, M. M. Rankin, R. Parsons, and M. F. White
Phosphatase and Tensin Homolog Regulation of Islet Growth and Glucose Homeostasis
J. Biol. Chem., November 25, 2005; 280(47): 39388 - 39393.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
K. Fukui, T. Wada, S. Kagawa, K. Nagira, M. Ikubo, H. Ishihara, M. Kobayashi, and T. Sasaoka
Impact of the Liver-Specific Expression of SHIP2 (SH2-Containing Inositol 5'-Phosphatase 2) on Insulin Signaling and Glucose Metabolism in Mice
Diabetes, July 1, 2005; 54(7): 1958 - 1967.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. Tang, A. M. Powelka, N. A. Soriano, M. P. Czech, and A. Guilherme
PTEN, but Not SHIP2, Suppresses Insulin Signaling through the Phosphatidylinositol 3-Kinase/Akt Pathway in 3T3-L1 Adipocytes
J. Biol. Chem., June 10, 2005; 280(23): 22523 - 22529.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
L. M. Watts, V. P. Manchem, T. A. Leedom, A. L. Rivard, R. A. McKay, D. Bao, T. Neroladakis, B. P. Monia, D. M. Bodenmiller, J. X.-C. Cao, et al.
Reduction of Hepatic and Adipose Tissue Glucocorticoid Receptor Expression With Antisense Oligonucleotides Improves Hyperglycemia and Hyperlipidemia in Diabetic Rodents Without Causing Systemic Glucocorticoid Antagonism
Diabetes, June 1, 2005; 54(6): 1846 - 1853.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
R. M. Crooke, M. J. Graham, K. M. Lemonidis, C. P. Whipple, S. Koo, and R. J. Perera
An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosis
J. Lipid Res., May 1, 2005; 46(5): 872 - 884.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. Kurlawalla-Martinez, B. Stiles, Y. Wang, S. U. Devaskar, B. B. Kahn, and H. Wu
Insulin Hypersensitivity and Resistance to Streptozotocin-Induced Diabetes in Mice Lacking PTEN in Adipose Tissue
Mol. Cell. Biol., March 15, 2005; 25(6): 2498 - 2510.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
N. Wijesekara, D. Konrad, M. Eweida, C. Jefferies, N. Liadis, A. Giacca, M. Crackower, A. Suzuki, T. W. Mak, C. R. Kahn, et al.
Muscle-Specific Pten Deletion Protects against Insulin Resistance and Diabetes
Mol. Cell. Biol., February 1, 2005; 25(3): 1135 - 1145.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
D. Drygin, S. Barone, and C. F. Bennett
Sequence-dependent cytotoxicity of second-generation oligonucleotides
Nucleic Acids Res., December 16, 2004; 32(22): 6585 - 6594.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
C.-L. Su, C.-H. Chen, H.-Y. Lu, and P.-W. Gean
The Involvement of PTEN in Sleep Deprivation-Induced Memory Impairment in Rats
Mol. Pharmacol., November 1, 2004; 66(5): 1340 - 1348.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Ueki, T. Kondo, Y.-H. Tseng, and C. R. Kahn
Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse
PNAS, July 13, 2004; 101(28): 10422 - 10427.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K. Ueki, T. Kondo, and C. R. Kahn
Suppressor of Cytokine Signaling 1 (SOCS-1) and SOCS-3 Cause Insulin Resistance through Inhibition of Tyrosine Phosphorylation of Insulin Receptor Substrate Proteins by Discrete Mechanisms
Mol. Cell. Biol., June 15, 2004; 24(12): 5434 - 5446.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Wu, W. F. Lima, H. Zhang, A. Fan, H. Sun, and S. T. Crooke
Determination of the Role of the Human RNase H1 in the Pharmacology of DNA-like Antisense Drugs
J. Biol. Chem., April 23, 2004; 279(17): 17181 - 17189.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. Stiles, Y. Wang, A. Stahl, S. Bassilian, W. P. Lee, Y.-J. Kim, R. Sherwin, S. Devaskar, R. Lesche, M. A. Magnuson, et al.
Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity
PNAS, February 17, 2004; 101(7): 2082 - 2087.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
Y. Liang, M. C. Osborne, B. P. Monia, S. Bhanot, W. A. Gaarde, C. Reed, P. She, T. L. Jetton, and K. T. Demarest
Reduction in Glucagon Receptor Expression by an Antisense Oligonucleotide Ameliorates Diabetic Syndrome in db/db Mice
Diabetes, February 1, 2004; 53(2): 410 - 417.
[Abstract] [Full Text]

Home page
 Hum Mol GenetHome page
D. C.I. Goberdhan and C. Wilson
PTEN: tumour suppressor, multifunctional growth regulator and more
Hum. Mol. Genet., October 15, 2003; 12(90002): R239 - 248.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Yahagi, H. Shimano, T. Matsuzaka, Y. Najima, M. Sekiya, Y. Nakagawa, T. Ide, S. Tomita, H. Okazaki, Y. Tamura, et al.
p53 Activation in Adipocytes of Obese Mice
J. Biol. Chem., July 3, 2003; 278(28): 25395 - 25400.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. A. Vickers, S. Koo, C. F. Bennett, S. T. Crooke, N. M. Dean, and B. F. Baker
Efficient Reduction of Target RNAs by Small Interfering RNA and RNase H-dependent Antisense Agents. A COMPARATIVE ANALYSIS
J. Biol. Chem., February 21, 2003; 278(9): 7108 - 7118.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2002 by the American Diabetes Association.