Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

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}

Local overexpression of the myostatin propeptide increases glucose transporter expression and enhances skeletal muscle glucose disposal.
M. E. Cleasby, S. Jarmin, W. Eilers, M. Elashry, D. K. Andersen, G. Dickson, and K. Foster (2014)
Am J Physiol Endocrinol Metab 306, E814-E823
   Abstract »    Full Text »    PDF »
Insulin signaling, resistance, and metabolic syndrome: insights from mouse models into disease mechanisms.
S. Guo (2014)
J. Endocrinol. 220, T1-T23
   Abstract »    Full Text »    PDF »
Akt2/LDLr double knockout mice display impaired glucose tolerance and develop more complex atherosclerotic plaques than LDLr knockout mice.
K. L. Rensing, S. C. A. de Jager, E. S. Stroes, M. Vos, M. T. B. Twickler, G. M. Dallinga-Thie, C. J. M. de Vries, J. Kuiper, I. Bot, and J. H. von der Thusen (2014)
Cardiovasc Res 101, 277-287
   Abstract »    Full Text »    PDF »
Cross Talk between Cellular Redox Status, Metabolism, and p53 in Neural Stem Cell Biology.
K. Forsberg and S. Di Giovanni (2014)
   Abstract »    Full Text »    PDF »
Regulation of Akt Signaling by Sirtuins: Its Implication in Cardiac Hypertrophy and Aging.
V. B. Pillai, N. R. Sundaresan, and M. P. Gupta (2014)
Circ. Res. 114, 368-378
   Abstract »    Full Text »    PDF »
Acute exercise and physiological insulin induce distinct phosphorylation signatures on TBC1D1 and TBC1D4 proteins in human skeletal muscle.
J. T. Treebak, C. Pehmoller, J. M. Kristensen, R. Kjobsted, J. B. Birk, P. Schjerling, E. A. Richter, L. J. Goodyear, and J. F. P. Wojtaszewski (2014)
J. Physiol. 592, 351-375
   Abstract »    Full Text »    PDF »
AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1.
D. G. Corum, P. N. Tsichlis, and R. C. Muise-Helmericks (2014)
FASEB J 28, 395-407
   Abstract »    Full Text »    PDF »
Insulin Receptor Signaling in Normal and Insulin-Resistant States.
J. Boucher, A. Kleinridders, and C. R. Kahn (2014)
Cold Spring Harb Perspect Biol 6, a009191
   Abstract »    Full Text »    PDF »
Rapamycin Induces Mitogen-activated Protein (MAP) Kinase Phosphatase-1 (MKP-1) Expression through Activation of Protein Kinase B and Mitogen-activated Protein Kinase Kinase Pathways.
R. Rastogi, Z. Jiang, N. Ahmad, R. Rosati, Y. Liu, L. Beuret, R. Monks, J. Charron, M. J. Birnbaum, and L. Samavati (2013)
J. Biol. Chem. 288, 33966-33977
   Abstract »    Full Text »    PDF »
Impact of embryo number and periconceptional undernutrition on factors regulating adipogenesis, lipogenesis, and metabolism in adipose tissuein the sheep fetus.
S. Lie, J. L. Morrison, O. Williams-Wyss, S. E. Ozanne, S. Zhang, S. K. Walker, D. O. Kleemann, S. M. MacLaughlin, C. T. Roberts, and I. C. McMillen (2013)
Am J Physiol Endocrinol Metab 305, E931-E941
   Abstract »    Full Text »    PDF »
Inhibition of Protein Synthesis Alters Protein Degradation through Activation of Protein Kinase B (AKT).
C.-L. Dai, J. Shi, Y. Chen, K. Iqbal, F. Liu, and C.-X. Gong (2013)
J. Biol. Chem. 288, 23875-23883
   Abstract »    Full Text »    PDF »
Lack of myotubularin (MTM1) leads to muscle hypotrophy through unbalanced regulation of the autophagy and ubiquitin-proteasome pathways.
L. Al-Qusairi, I. Prokic, L. Amoasii, C. Kretz, N. Messaddeq, J.-L. Mandel, and J. Laporte (2013)
FASEB J 27, 3384-3394
   Abstract »    Full Text »    PDF »
Saturated and unsaturated fat induce hepatic insulin resistance independently of TLR-4 signaling and ceramide synthesis in vivo.
T. Galbo, R. J. Perry, M. J. Jurczak, J.-P. G. Camporez, T. C. Alves, M. Kahn, B. A. Guigni, J. Serr, D. Zhang, S. Bhanot, et al. (2013)
PNAS 110, 12780-12785
   Abstract »    Full Text »    PDF »
Lack of Oncostatin M Receptor {beta} Leads to Adipose Tissue Inflammation and Insulin Resistance by Switching Macrophage Phenotype.
T. Komori, M. Tanaka, E. Senba, A. Miyajima, and Y. Morikawa (2013)
J. Biol. Chem. 288, 21861-21875
   Abstract »    Full Text »    PDF »
Enhanced Fasting Glucose Turnover in Mice with Disrupted Action of TUG Protein in Skeletal Muscle.
M. G. Loffler, A. L. Birkenfeld, K. M. Philbrick, J. P. Belman, E. N. Habtemichael, C. J. Booth, C. M. Castorena, C. S. Choi, F. R. Jornayvaz, B. M. Gassaway, et al. (2013)
J. Biol. Chem. 288, 20135-20150
   Abstract »    Full Text »    PDF »
Muscle-specific Pikfyve gene disruption causes glucose intolerance, insulin resistance, adiposity, and hyperinsulinemia but not muscle fiber-type switching.
O. C. Ikonomov, D. Sbrissa, K. Delvecchio, H.-Z. Feng, G. D. Cartee, J.-P. Jin, and A. Shisheva (2013)
Am J Physiol Endocrinol Metab 305, E119-E131
   Abstract »    Full Text »    PDF »
New Approaches to Prevent LEOPARD Syndrome-associated Cardiac Hypertrophy by Specifically Targeting Shp2-dependent Signaling.
C. Schramm, M. A. Edwards, and M. Krenz (2013)
J. Biol. Chem. 288, 18335-18344
   Abstract »    Full Text »    PDF »
Rac-1 Superactivation Triggers Insulin-independent Glucose Transporter 4 (GLUT4) Translocation That Bypasses Signaling Defects Exerted by c-Jun N-terminal kinase (JNK)- and Ceramide-induced Insulin Resistance.
T. T. Chiu, Y. Sun, A. Koshkina, and A. Klip (2013)
J. Biol. Chem. 288, 17520-17531
   Abstract »    Full Text »    PDF »
Interaction of Constitutive Photomorphogenesis 1 Protein with Protein-Tyrosine Phosphatase 1B Suppresses Protein-Tyrosine Phosphatase 1B Activity and Enhances Insulin Signaling.
W. Ren, Y. Sun, S. Cheema, and K. Du (2013)
J. Biol. Chem. 288, 10902-10913
   Abstract »    Full Text »    PDF »
Akt2 influences glycogen synthase activity in human skeletal muscle through regulation of NH2-terminal (sites 2 + 2a) phosphorylation.
M. Friedrichsen, J. B. Birk, E. A. Richter, R. Ribel-Madsen, C. Pehmoller, B. F. Hansen, H. Beck-Nielsen, M. F. Hirshman, L. J. Goodyear, A. Vaag, et al. (2013)
Am J Physiol Endocrinol Metab 304, E631-E639
   Abstract »    Full Text »    PDF »
Suppression of Inflammatory Responses during Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis Is Regulated by AKT3 Signaling.
V. Tsiperson, R. C. Gruber, M. F. Goldberg, A. Jordan, J. G. Weinger, F. Macian, and B. Shafit-Zagardo (2013)
J. Immunol. 190, 1528-1539
   Abstract »    Full Text »    PDF »
AKT2 Confers Protection Against Aortic Aneurysms and Dissections.
Y. H. Shen, L. Zhang, P. Ren, M. T. Nguyen, S. Zou, D. Wu, X. L. Wang, J. S. Coselli, and S. A. LeMaire (2013)
Circ. Res. 112, 618-632
   Abstract »    Full Text »    PDF »
Akt1 promotes focal adhesion disassembly and cell motility through phosphorylation of FAK in growth factor-stimulated cells.
M. Higuchi, R. Kihara, T. Okazaki, I. Aoki, S. Suetsugu, and Y. Gotoh (2013)
J. Cell Sci. 126, 745-755
   Abstract »    Full Text »    PDF »
Elovl5 regulates the mTORC2-Akt-FOXO1 pathway by controlling hepatic cis-vaccenic acid synthesis in diet-induced obese mice.
S. Tripathy and D. B. Jump (2013)
J. Lipid Res. 54, 71-84
   Abstract »    Full Text »    PDF »
Calorie Restriction Enhances Insulin-Stimulated Glucose Uptake and Akt Phosphorylation in Both Fast-Twitch and Slow-Twitch Skeletal Muscle of 24-Month-Old Rats.
D. A. Sequea, N. Sharma, E. B. Arias, and G. D. Cartee (2012)
J Gerontol A Biol Sci Med Sci 67, 1279-1285
   Abstract »    Full Text »    PDF »
Disruption of Growth Factor Receptor-Binding Protein 10 in the Pancreas Enhances {beta}-Cell Proliferation and Protects Mice From Streptozotocin-Induced {beta}-Cell Apoptosis.
J. Zhang, N. Zhang, M. Liu, X. Li, L. Zhou, W. Huang, Z. Xu, J. Liu, N. Musi, R. A. DeFronzo, et al. (2012)
Diabetes 61, 3189-3198
   Abstract »    Full Text »    PDF »
Disassociation of insulin action and Akt/FOXO signaling in skeletal muscle of older Akt-deficient mice.
T. H. Reynolds 4th, E. Merrell, N. Cinquino, M. Gaugler, and L. Ng (2012)
Am J Physiol Regulatory Integrative Comp Physiol 303, R1186-R1194
   Abstract »    Full Text »    PDF »
mTOR-Dependent Cell Survival Mechanisms.
C.-M. Hung, L. Garcia-Haro, C. A. Sparks, and D. A. Guertin (2012)
Cold Spring Harb Perspect Biol 4, a008771
   Abstract »    Full Text »    PDF »
The Inflammatory Chemokine CXC Motif Ligand 16 Triggers Platelet Activation and Adhesion Via CXC Motif Receptor 6-Dependent Phosphatidylinositide 3-Kinase/Akt Signaling.
O. Borst, P. Munzer, S. Gatidis, E.-M. Schmidt, T. Schonberger, E. Schmid, S. T. Towhid, K. Stellos, P. Seizer, A. E. May, et al. (2012)
Circ. Res. 111, 1297-1307
   Abstract »    Full Text »    PDF »
The Combined Deletion of S6K1 and Akt2 Deteriorates Glycemic Control in a High-Fat Diet.
C. Treins, S. Alliouachene, R. Hassouna, Y. Xie, M. J. Birnbaum, and M. Pende (2012)
Mol. Cell. Biol. 32, 4001-4011
   Abstract »    Full Text »    PDF »
Autocrine prolactin induced by the Pten-Akt pathway is required for lactation initiation and provides a direct link between the Akt and Stat5 pathways.
C.-C. Chen, D. B. Stairs, R. B. Boxer, G. K. Belka, N. D. Horseman, J. V. Alvarez, and L. A. Chodosh (2012)
Genes & Dev. 26, 2154-2168
   Abstract »    Full Text »    PDF »
The Akt1 Isoform Is Required for Optimal IFN-{beta} Transcription through Direct Phosphorylation of {beta}-Catenin.
B. N. Gantner, H. Jin, F. Qian, N. Hay, B. He, and R. D. Ye (2012)
J. Immunol. 189, 3104-3111
   Abstract »    Full Text »    PDF »
Obesity, insulin resistance, and skeletal muscle nitric oxide synthase.
R. M. Kraus, J. A. Houmard, W. E. Kraus, C. J. Tanner, J. R. Pierce, M. D. Choi, and R. C. Hickner (2012)
J Appl Physiol 113, 758-765
   Abstract »    Full Text »    PDF »
Regulation of Insulin Signaling by the Phosphatidylinositol 3,4,5-Triphosphate Phosphatase SKIP through the Scaffolding Function of Pak1.
T. Ijuin and T. Takenawa (2012)
Mol. Cell. Biol. 32, 3570-3584
   Abstract »    Full Text »    PDF »
Human {beta}-Cell Proliferation and Intracellular Signaling: Driving in the Dark Without a Road Map.
R. N. Kulkarni, E.-B. Mizrachi, A. G. Ocana, and A. F. Stewart (2012)
Diabetes 61, 2205-2213
   Abstract »    Full Text »    PDF »
Identification of Akt-independent Regulation of Hepatic Lipogenesis by Mammalian Target of Rapamycin (mTOR) Complex 2.
M. Yuan, E. Pino, L. Wu, M. Kacergis, and A. A. Soukas (2012)
J. Biol. Chem. 287, 29579-29588
   Abstract »    Full Text »    PDF »
Nesfatin-1 Action in the Brain Increases Insulin Sensitivity Through Akt/AMPK/TORC2 Pathway in Diet-Induced Insulin Resistance.
M. Yang, Z. Zhang, C. Wang, K. Li, S. Li, G. Boden, L. Li, and G. Yang (2012)
Diabetes 61, 1959-1968
   Abstract »    Full Text »    PDF »
Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization.
A. Arranz, C. Doxaki, E. Vergadi, Y. Martinez de la Torre, K. Vaporidi, E. D. Lagoudaki, E. Ieronymaki, A. Androulidaki, M. Venihaki, A. N. Margioris, et al. (2012)
PNAS 109, 9517-9522
   Abstract »    Full Text »    PDF »
Perifosine-mediated Akt inhibition in neuroendocrine tumor cells: role of specific Akt isoforms.
K. Zitzmann, G. Vlotides, S. Brand, H. Lahm, G. Spottl, B. Goke, and C. J. Auernhammer (2012)
Endocr. Relat. Cancer 19, 423-434
   Abstract »    Full Text »    PDF »
Loss of PKB{beta}/Akt2 predisposes mice to ovarian cyst formation and increases the severity of polycystic ovary formation in vivo.
D. F. Restuccia, D. Hynx, and B. A. Hemmings (2012)
Dis. Model. Mech. 5, 403-411
   Abstract »    Full Text »    PDF »
TLR4-Mediated AKT Activation Is MyD88/TRIF Dependent and Critical for Induction of Oxidative Phosphorylation and Mitochondrial Transcription Factor A in Murine Macrophages.
C. P. Bauerfeld, R. Rastogi, G. Pirockinaite, I. Lee, M. Huttemann, B. Monks, M. J. Birnbaum, L. Franchi, G. Nunez, and L. Samavati (2012)
J. Immunol. 188, 2847-2857
   Abstract »    Full Text »    PDF »
Regulation of Insulin Signaling and Glucose Transporter 4 (GLUT4) Exocytosis by Phosphatidylinositol 3,4,5-Trisphosphate (PIP3) Phosphatase, Skeletal Muscle, and Kidney Enriched Inositol Polyphosphate Phosphatase (SKIP).
T. Ijuin and T. Takenawa (2012)
J. Biol. Chem. 287, 6991-6999
   Abstract »    Full Text »    PDF »
Amplification and Demultiplexing in Insulin-regulated Akt Protein Kinase Pathway in Adipocytes.
S.-X. Tan, Y. Ng, C. C. Meoli, A. Kumar, P.-S. Khoo, D. J. Fazakerley, J. R. Junutula, S. Vali, D. E. James, and J. Stockli (2012)
J. Biol. Chem. 287, 6128-6138
   Abstract »    Full Text »    PDF »
Insulin Augmentation of Glucose-Stimulated Insulin Secretion Is Impaired in Insulin-Resistant Humans.
F. Halperin, X. Lopez, R. Manning, C. R. Kahn, R. N. Kulkarni, and A. B. Goldfine (2012)
Diabetes 61, 301-309
   Abstract »    Full Text »    PDF »
Selective Signaling by Akt1 Controls Osteoblast Differentiation and Osteoblast-Mediated Osteoclast Development.
A. Mukherjee and P. Rotwein (2012)
Mol. Cell. Biol. 32, 490-500
   Abstract »    Full Text »    PDF »
Loss of Akt1 in Mice Increases Energy Expenditure and Protects against Diet-Induced Obesity.
M. Wan, R. M. Easton, C. E. Gleason, B. R. Monks, K. Ueki, C. R. Kahn, and M. J. Birnbaum (2012)
Mol. Cell. Biol. 32, 96-106
   Abstract »    Full Text »    PDF »
Chronic Akt blockade aggravates pathological hypertrophy and inhibits physiological hypertrophy.
S. J. Buss, J. H. Riffel, P. Malekar, M. Hagenmueller, C. Asel, M. Zhang, C. Weiss, H. A. Katus, and S. E. Hardt (2012)
Am J Physiol Heart Circ Physiol 302, H420-H430
   Abstract »    Full Text »    PDF »
Regulation, Role, and Targeting of Akt in Cancer.
M. A. Davies (2011)
J. Clin. Oncol. 29, 4715-4717
   Full Text »    PDF »
First-in-Man Clinical Trial of the Oral Pan-AKT Inhibitor MK-2206 in Patients With Advanced Solid Tumors.
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)
J. Clin. Oncol. 29, 4688-4695
   Abstract »    Full Text »    PDF »
FOSL1 Is Integral to Establishing the Maternal-Fetal Interface.
L. N. Kent, M. A. K. Rumi, K. Kubota, D.-S. Lee, and M. J. Soares (2011)
Mol. Cell. Biol. 31, 4801-4813
   Abstract »    Full Text »    PDF »
Targeting AKT Protein Kinase in Gastric Cancer.
Anticancer Res 31, 4387-4392
   Abstract »    Full Text »    PDF »
Pancreatic {beta}-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcription.
E. U. Alejandro, G. E. Lim, A. E. Mehran, X. Hu, F. Taghizadeh, D. Pelipeychenko, M. Baccarini, and J. D. Johnson (2011)
FASEB J 25, 3884-3895
   Abstract »    Full Text »    PDF »
TRB3 Gene Silencing Alleviates Diabetic Cardiomyopathy in a Type 2 Diabetic Rat Model.
Y. Ti, G.-l. Xie, Z.-h. Wang, X.-l. Bi, W.-y. Ding, J. Wang, G.-h. Jiang, P.-l. Bu, Y. Zhang, M. Zhong, et al. (2011)
Diabetes 60, 2963-2974
   Abstract »    Full Text »    PDF »
Myocardial injury after ischemia-reperfusion in mice deficient in Akt2 is associated with increased cardiac macrophage density.
X. Li, D. Mikhalkova, E. Gao, J. Zhang, V. Myers, C. Zincarelli, Y. Lei, J. Song, W. J. Koch, K. Peppel, et al. (2011)
Am J Physiol Heart Circ Physiol 301, H1932-H1940
   Abstract »    Full Text »    PDF »
An Activating Mutation of AKT2 and Human Hypoglycemia.
K. Hussain, B. Challis, N. Rocha, F. Payne, M. Minic, A. Thompson, A. Daly, C. Scott, J. Harris, B. J. L. Smillie, et al. (2011)
Science 334, 474
   Abstract »    Full Text »    PDF »
mSIN1 Protein Mediates SGK1 Protein Interaction with mTORC2 Protein Complex and Is Required for Selective Activation of the Epithelial Sodium Channel.
M. Lu, J. Wang, H. E. Ives, and D. Pearce (2011)
J. Biol. Chem. 286, 30647-30654
   Abstract »    Full Text »    PDF »
Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes.
M. Ito, M. Nagasawa, N. Omae, T. Ide, Y. Akasaka, and K. Murakami (2011)
J. Lipid Res. 52, 1450-1460
   Abstract »    Full Text »    PDF »
AKT signalling in the failing heart.
A. H. Chaanine and R. J. Hajjar (2011)
Eur J Heart Fail 13, 825-829
   Abstract »    Full Text »    PDF »
A Cyp2a polymorphism predicts susceptibility to NNK-induced lung tumorigenesis in mice.
M. C. Hollander, X. Zhou, C. R. Maier, A. D. Patterson, X. Ding, and P. A. Dennis (2011)
Carcinogenesis 32, 1279-1284
   Abstract »    Full Text »    PDF »
The adaptor protein APPL1 increases glycogen accumulation in rat skeletal muscle through activation of the PI3-kinase signalling pathway.
M. E. Cleasby, Q. Lau, E. Polkinghorne, S. A. Patel, S. J. Leslie, N. Turner, G. J. Cooney, A. Xu, and E. W. Kraegen (2011)
J. Endocrinol. 210, 81-92
   Abstract »    Full Text »    PDF »
Myocardial AKT: The Omnipresent Nexus.
M. A. Sussman, M. Volkers, K. Fischer, B. Bailey, C. T. Cottage, S. Din, N. Gude, D. Avitabile, R. Alvarez, B. Sundararaman, et al. (2011)
Physiol Rev 91, 1023-1070
   Abstract »    Full Text »    PDF »
Protective Role of Akt2 in Salmonella enterica Serovar Typhimurium-Induced Gastroenterocolitis.
W. W. S. Kum, B. C. Lo, H. B. Yu, and B. B. Finlay (2011)
Infect. Immun. 79, 2554-2566
   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)
PNAS 108, 10162-10167
   Abstract »    Full Text »    PDF »
Nonredundant Functions for Akt Isoforms in Astrocyte Growth and Gliomagenesis in an Orthotopic Transplantation Model.
R. Endersby, X. Zhu, N. Hay, D. W. Ellison, and S. J. Baker (2011)
Cancer Res. 71, 4106-4116
   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 »
Dysfunctional ryanodine receptor and cardiac hypertrophy: role of signaling molecules.
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 »
Feather pecking behavior in laying hens: Hypothalamic gene expression in birds performing and receiving pecks.
E. Brunberg, P. Jensen, A. Isaksson, and L. Keeling (2011)
Poultry Science 90, 1145-1152
   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 »
A novel Akt3 mutation associated with enhanced kinase activity and seizure susceptibility in mice.
S. Tokuda, C. L. Mahaffey, B. Monks, C. R. Faulkner, M. J. Birnbaum, S. C. Danzer, and W. N. Frankel (2011)
Hum. Mol. Genet. 20, 988-999
   Abstract »    Full Text »    PDF »
ER Stress Inhibits mTORC2 and Akt Signaling Through GSK-3{beta}-Mediated Phosphorylation of Rictor.
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)
Science Signaling 4, ra10
   Abstract »    Full Text »    PDF »
Insulin Receptor Substrates Irs1 and Irs2 Coordinate Skeletal Muscle Growth and Metabolism via the Akt and AMPK Pathways.
Y. C. Long, Z. Cheng, K. D. Copps, and M. F. White (2011)
Mol. Cell. Biol. 31, 430-441
   Abstract »    Full Text »    PDF »
Uremic Cardiomyopathy and Insulin Resistance: A Critical Role for Akt?.
D. Semple, K. Smith, S. Bhandari, and A.-M. L. Seymour (2011)
J. Am. Soc. Nephrol. 22, 207-215
   Abstract »    Full Text »    PDF »
The WNKs: Atypical Protein Kinases With Pleiotropic Actions.
J. A. McCormick and D. H. Ellison (2011)
Physiol Rev 91, 177-219
   Abstract »    Full Text »    PDF »
Prenatal hypoxia independent of undernutrition promotes molecular markers of insulin resistance in adult offspring.
E. J. Camm, M. S. Martin-Gronert, N. L. Wright, J. A. Hansell, S. E. Ozanne, and D. A. Giussani (2011)
FASEB J 25, 420-427
   Abstract »    Full Text »    PDF »
Calcineurin Signaling Regulates Human Islet {beta}-Cell Survival.
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)
J. Biol. Chem. 285, 40050-40059
   Abstract »    Full Text »    PDF »
Insulin Regulates Adipocyte Lipolysis via an Akt-Independent Signaling Pathway.
S. M. Choi, D. F. Tucker, D. N. Gross, R. M. Easton, L. M. DiPilato, A. S. Dean, B. R. Monks, and M. J. Birnbaum (2010)
Mol. Cell. Biol. 30, 5009-5020
   Abstract »    Full Text »    PDF »
From man to mouse and back again: advances in defining tumor AKTivities in vivo.
D. F. Restuccia and B. A. Hemmings (2010)
Dis. Model. Mech. 3, 705-720
   Abstract »    Full Text »    PDF »
Activation of Akt Is Essential for the Propagation of Mitochondrial Respiratory Stress Signaling and Activation of the Transcriptional Coactivator Heterogeneous Ribonucleoprotein A2.
M. Guha, J.-K. Fang, R. Monks, M. J. Birnbaum, and N. G. Avadhani (2010)
Mol. Biol. Cell 21, 3578-3589
   Abstract »    Full Text »    PDF »
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
   Full Text »    PDF »
Akt isoforms differentially regulate neutrophil functions.
J. Chen, H. Tang, N. Hay, J. Xu, and R. D. Ye (2010)
Blood 115, 4237-4246
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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 »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882