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Science 292 (5522): 1728-1731

Copyright © 2001 by the American Association for the Advancement of Science

Insulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBbeta )

Han Cho,1 James Mu,26 Jason K. Kim,67 Joanne L. Thorvaldsen,36 Qingwei Chu,26 E. Bryan Crenshaw III,4 Klaus H. Kaestner,5 Marisa S. Bartolomei,36 Gerald I. Shulman,67 Morris J. Birnbaum26*

Glucose homeostasis depends on insulin responsiveness in target tissues, most importantly, muscle and liver. The critical initial steps in insulin action include phosphorylation of scaffolding proteins and activation of phosphatidylinositol 3-kinase. These early events lead to activation of the serine-threonine protein kinase Akt, also known as protein kinase B. We show that mice deficient in Akt2 are impaired in the ability of insulin to lower blood glucose because of defects in the action of the hormone on liver and skeletal muscle. These data establish Akt2 as an essential gene in the maintenance of normal glucose homeostasis.

1 Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
2 Department of Medicine,
3 Department of Cell and Developmental Biology,
4 Department of Neuroscience, and
5 Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
6 Howard Hughes Medical Institute and the
7 Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
*   To whom correspondence should be addressed. E-mail: birnbaum{at}mail.med.upenn.edu


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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Full Text »    PDF »
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T. A. Yap, L. Yan, A. Patnaik, I. Fearen, D. Olmos, K. Papadopoulos, R. D. Baird, L. Delgado, A. Taylor, L. Lupinacci, et al. (2011)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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W. W. S. Kum, B. C. Lo, H. B. Yu, and B. B. Finlay (2011)
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   Abstract »    Full Text »    PDF »
Hyperinsulinemia leads to uncoupled insulin regulation of the GLUT4 glucose transporter and the FoxO1 transcription factor.
E. Gonzalez, E. Flier, D. Molle, D. Accili, and T. E. McGraw (2011)
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   Abstract »    Full Text »    PDF »
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R. Endersby, X. Zhu, N. Hay, D. W. Ellison, and S. J. Baker (2011)
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   Abstract »    Full Text »    PDF »
Mechanisms for increased insulin-stimulated Akt phosphorylation and glucose uptake in fast- and slow-twitch skeletal muscles of calorie-restricted rats.
N. Sharma, E. B. Arias, A. D. Bhat, D. A. Sequea, S. Ho, K. K. Croff, M. P. Sajan, R. V. Farese, and G. D. Cartee (2011)
Am J Physiol Endocrinol Metab 300, E966-E978
   Abstract »    Full Text »    PDF »
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N. Yamaguchi, A. Chakraborty, D. A. Pasek, J. D. Molkentin, and G. Meissner (2011)
Am J Physiol Heart Circ Physiol 300, H2187-H2195
   Abstract »    Full Text »    PDF »
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E. Brunberg, P. Jensen, A. Isaksson, and L. Keeling (2011)
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   Abstract »    Full Text »    PDF »
Modification of Akt1 by methylglyoxal promotes the proliferation of vascular smooth muscle cells.
T. Chang, R. Wang, D. J. H. Olson, D. D. Mousseau, A. R. S. Ross, and L. Wu (2011)
FASEB J 25, 1746-1757
   Abstract »    Full Text »    PDF »
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S. Tokuda, C. L. Mahaffey, B. Monks, C. R. Faulkner, M. J. Birnbaum, S. C. Danzer, and W. N. Frankel (2011)
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   Abstract »    Full Text »    PDF »
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C.-H. Chen, T. Shaikenov, T. R. Peterson, R. Aimbetov, A. K. Bissenbaev, S.-W. Lee, J. Wu, H.-K. Lin, and D. D. Sarbassov (2011)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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E. J. Camm, M. S. Martin-Gronert, N. L. Wright, J. A. Hansell, S. E. Ozanne, and D. A. Giussani (2011)
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   Abstract »    Full Text »    PDF »
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S. A. Soleimanpour, M. F. Crutchlow, A. M. Ferrari, J. C. Raum, D. N. Groff, M. M. Rankin, C. Liu, D. D. De Leon, A. Naji, J. A. Kushner, et al. (2010)
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A Novel Pleckstrin Homology Domain-containing Protein Enhances Insulin-stimulated Akt Phosphorylation and GLUT4 Translocation in Adipocytes.
Q. L. Zhou, Z. Y. Jiang, A. S. Mabardy, C. M. Del Campo, D. G. Lambright, J. Holik, K. E. Fogarty, J. Straubhaar, S. Nicoloro, A. Chawla, et al. (2010)
J. Biol. Chem. 285, 27581-27589
   Abstract »    Full Text »    PDF »
Identification and validation of the pathways and functions regulated by the orphan nuclear receptor, ROR alpha1, in skeletal muscle.
S. Raichur, R. L. Fitzsimmons, S. A. Myers, M. A. Pearen, P. Lau, N. Eriksson, S. M. Wang, and G. E. O. Muscat (2010)
Nucleic Acids Res. 38, 4296-4312
   Abstract »    Full Text »    PDF »
Akt2 Modulates Glucose Availability and Downstream Apoptotic Pathways during Development.
P. J. Jensen, L. B. Gunter, and M. O. Carayannopoulos (2010)
J. Biol. Chem. 285, 17673-17680
   Abstract »    Full Text »    PDF »
Hepatitis C virus genotype-3a core protein enhances sterol regulatory element-binding protein-1 activity through the phosphoinositide 3-kinase-Akt-2 pathway.
C. Jackel-Cram, L. Qiao, Z. Xiang, R. Brownlie, Y. Zhou, L. Babiuk, and Q. Liu (2010)
J. Gen. Virol. 91, 1388-1395
   Abstract »    Full Text »    PDF »
Insulin resistance for glucose uptake and Akt2 phosphorylation in the soleus, but not epitrochlearis, muscles of old vs. adult rats.
N. Sharma, E. B. Arias, M. P. Sajan, J. G. MacKrell, A. D. Bhat, R. V. Farese, and G. D. Cartee (2010)
J Appl Physiol 108, 1631-1640
   Abstract »    Full Text »    PDF »
Does obesity reduce load-induced muscle hypertrophy?.
M. R. Papasani, K. Thornton, Z. Yinggian, A. Brezas, C. Welch, G. Wang, A. Villasante, D. Pokharel, P. Cheguru, S. Kotla, et al. (2010)
J. Physiol. 588, 1819-1820
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Akt isoforms differentially regulate neutrophil functions.
J. Chen, H. Tang, N. Hay, J. Xu, and R. D. Ye (2010)
Blood 115, 4237-4246
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AKT1 and AKT2 maintain hematopoietic stem cell function by regulating reactive oxygen species.
M. M. Juntilla, V. D. Patil, M. Calamito, R. P. Joshi, M. J. Birnbaum, and G. A. Koretzky (2010)
Blood 115, 4030-4038
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Akt1 and Akt2 promote peripheral B-cell maturation and survival.
M. Calamito, M. M. Juntilla, M. Thomas, D. L. Northrup, J. Rathmell, M. J. Birnbaum, G. Koretzky, and D. Allman (2010)
Blood 115, 4043-4050
   Abstract »    Full Text »    PDF »
Isoform-specific Regulation of Akt Signaling by the Endosomal Protein WDFY2.
H. A. Walz, X. Shi, M. Chouinard, C. A. Bue, D. M. Navaroli, A. Hayakawa, Q. L. Zhou, J. Nadler, D. M. Leonard, and S. Corvera (2010)
J. Biol. Chem. 285, 14101-14108
   Abstract »    Full Text »    PDF »
Regulation of renal tubular glucose reabsorption by Akt2/PKB{beta}.
D. S. Kempe, G. Siraskar, H. Frohlich, A. T. Umbach, M. Stubs, F. Weiss, T. F. Ackermann, H. Volkl, M. J. Birnbaum, D. Pearce, et al. (2010)
Am J Physiol Renal Physiol 298, F1113-F1117
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Deficiency of Phosphoinositide 3-Kinase Enhancer Protects Mice From Diet-Induced Obesity and Insulin Resistance.
C. B. Chan, X. Liu, D. Y. Jung, J. Y. Jun, H. R. Luo, J. K. Kim, and K. Ye (2010)
Diabetes 59, 883-893
   Abstract »    Full Text »    PDF »
Insulin enhances glucose-stimulated insulin secretion in healthy humans.
C. Bouche, X. Lopez, A. Fleischman, A. M. Cypess, S. O'Shea, D. Stefanovski, R. N. Bergman, E. Rogatsky, D. T. Stein, C. R. Kahn, et al. (2010)
PNAS 107, 4770-4775
   Abstract »    Full Text »    PDF »
Akt2 and Akt3 play a pivotal role in malignant gliomas.
H. Mure, K. Matsuzaki, K. T. Kitazato, Y. Mizobuchi, K. Kuwayama, T. Kageji, and S. Nagahiro (2010)
Neuro Oncology 12, 221-232
   Abstract »    Full Text »    PDF »
Appl1 Is Dispensable for Mouse Development, and Loss of Appl1 Has Growth Factor-selective Effects on Akt Signaling in Murine Embryonic Fibroblasts.
Y. Tan, H. You, C. Wu, D. A. Altomare, and J. R. Testa (2010)
J. Biol. Chem. 285, 6377-6389
   Abstract »    Full Text »    PDF »
The PI3K Pathway As Drug Target in Human Cancer.
K. D. Courtney, R. B. Corcoran, and J. A. Engelman (2010)
J. Clin. Oncol. 28, 1075-1083
   Abstract »    Full Text »    PDF »

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