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Citations to this article

Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKBβ
Robert S. Garofalo, … , John D. McNeish, Kevin G. Coleman
Robert S. Garofalo, … , John D. McNeish, Kevin G. Coleman
Published July 15, 2003
Citation Information: J Clin Invest. 2003;112(2):197-208. https://doi.org/10.1172/JCI16885.
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Article Metabolism Article has an altmetric score of 12

Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKBβ

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Abstract

The serine/threonine kinase Akt/PKB plays key roles in the regulation of cell growth, survival, and metabolism. It remains unclear, however, whether the functions of individual Akt/PKB isoforms are distinct. To investigate the function of Akt2/PKBβ, mice lacking this isoform were generated. Both male and female Akt2/PKBβ-null mice exhibit mild growth deficiency and an age-dependent loss of adipose tissue or lipoatrophy, with all observed adipose depots dramatically reduced by 22 weeks of age. Akt2/PKBβ-deficient mice are insulin resistant with elevated plasma triglycerides. In addition, Akt2/PKBβ-deficient mice exhibit fed and fasting hyperglycemia, hyperinsulinemia, glucose intolerance, and impaired muscle glucose uptake. In males, insulin resistance progresses to a severe form of diabetes accompanied by pancreatic β cell failure. In contrast, female Akt2/PKBβ-deficient mice remain mildly hyperglycemic and hyperinsulinemic until at least one year of age. Thus, Akt2/PKBβ-deficient mice exhibit growth deficiency similar to that reported previously for mice lacking Akt1/PKBα, indicating that both Akt2/PKBβ and Akt1/PKBα participate in the regulation of growth. The marked hyperglycemia and loss of pancreatic β cells and adipose tissue in Akt2/PKBβ-deficient mice suggest that Akt2/PKBβ plays critical roles in glucose metabolism and the development or maintenance of proper adipose tissue and islet mass for which other Akt/PKB isoforms are unable to fully compensate.

Authors

Robert S. Garofalo, Stephen J. Orena, Kristina Rafidi, Anthony J. Torchia, Jeffrey L. Stock, Audrey L. Hildebrandt, Timothy Coskran, Shawn C. Black, Dominique J. Brees, Joan R. Wicks, John D. McNeish, Kevin G. Coleman

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 Total
Citations: 4 9 9 9 19 14 19 11 22 10 24 23 24 27 25 18 20 14 7 8 7 6 2 331
Citation information
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Citations to this article in year 2011 (25)

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Non-redundant functions for Akt isoforms in astrocyte growth and gliomagenesis in an orthotopic transplantation model
R Endersby, X Zhu, N Hay, DW Ellison, SJ Baker
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Akt2 regulates all Akt isoforms and promotes resistance to hypoxia through induction of miR-21 upon oxygen deprivation
C Polytarchou, D Iliopoulos, M Hatziapostolou, F Kottakis, I Maroulakou, K Struhl, PN Tsichlis
Cancer research 2011
Myocardial AKT: the omnipresent nexus
MA Sussman, M Völkers, K Fischer, B Bailey, CT Cottage, S Din, N Gude, D Avitabile, R Alvarez, B Sundararaman, P Quijada, M Mason, MH Konstandin, A Malhowski, Z Cheng, M Khan, M McGregor
Physiological reviews 2011
Loss of Akt1 in Mice Increases Energy Expenditure and Protects against Diet-Induced Obesity
M Wan, RM Easton, CE Gleason, BR Monks, K Ueki, CR Kahn, MJ Birnbaum
Molecular and cellular biology 2011
The role of mammalian target of rapamycin (mTOR) in the regulation of pancreatic β-cell mass: implications in the development of type-2 diabetes
J Xie, TP Herbert
Cellular and Molecular Life Sciences 2011
Akt Stimulates Hepatic SREBP1c and Lipogenesis through Parallel mTORC1-Dependent and Independent Pathways
JL Yecies, HH Zhang, S Menon, S Liu, D Yecies, AI Lipovsky, C Gorgun, DJ Kwiatkowski, GS Hotamisligil, CH Lee, BD Manning
Cell Metabolism 2011
Ipomoea batatas and Agarics blazei ameliorate diabetic disorders with therapeutic antioxidant potential in streptozotocin-induced diabetic rats
A Niwa, T Tajiri, H Higashino
Journal of Clinical Biochemistry and Nutrition 2011
Therapeutic Implications of Targeting AKT Signaling in Melanoma
SV Madhunapantula, GP Robertson
Enzyme Research 2011
Homozygous staggerer (sg/sg) mice display improved insulin sensitivity and enhanced glucose uptake in skeletal muscle
P Lau, RL Fitzsimmons, MA Pearen, MJ Watt, GE Muscat
Diabetologia 2011
The effect of high-intensity intermittent swimming on post-exercise glycogen supercompensation in rat skeletal muscle
A Sano, K Koshinaka, N Abe, M Morifuji, J Koga, E Kawasaki, K Kawanaka
The Journal of Physiological Sciences 2011
Obestatin as a regulator of adipocyte metabolism and adipogenesis
U Gurriarán-Rodríguez, O Al-Massadi, A Roca-Rivada, AB Crujeiras, R Gallego, M Pardo, LM Seoane, Y Pazos, FF Casanueva, JP Camiña
Journal of Cellular and Molecular Medicine 2011
An important role for Akt3 in platelet activation and thrombosis
KA O'Brien, A Stojanovic-Terpo, N Hay, X Du
Blood 2011
The effect Akt2 deletion on tumor development in Pten+/− mice
PZ Xu, ML Chen, SM Jeon, X Peng, N Hay
Oncogene 2011
Adiponectin Inhibits Osteoclastogenesis and Bone Resorption via APPL1-mediated Suppression of Akt1*
Q Tu, J Zhang, LQ Dong, E Saunders, E Luo, J Tang, J Chen
The Journal of biological chemistry 2011
Hyperinsulinemia leads to uncoupled insulin regulation of the GLUT4 glucose transporter and the FoxO1 transcription factor
E Gonzalez, E Flier, D Molle, D Accili, TE McGraw
Proceedings of the National Academy of Sciences 2011
Hepatic response to oxidative injury in long-lived Ames dwarf mice
LY Sun, AF Bokov, A Richardson, RA Miller
The FASEB Journal 2011
Environmental contaminants: Is male reproductive health at risk?
DD Mruk, CY Cheng
Spermatogenesis 2011
Akt1 protects against germ cell apoptosis in the postnatal mouse testis following lactational exposure to 6-N-propylthiouracil
J Santos-Ahmed, C Brown, SD Smith, P Weston, T Rasoulpour, ME Gilbert, ML Hixon
Reproductive Toxicology 2011
Inhibition of Akt with small molecules and biologics: historical perspective and current status of the patent landscape
ME Mattmann, SL Stoops, CW Lindsley
Expert Opinion on Therapeutic Patents 2011
The Regulation of Skeletal Muscle Protein Turnover during the Progression of Cancer Cachexia in the ApcMin/+ Mouse
JP White, JW Baynes, SL Welle, MC Kostek, LE Matesic, S Sato, JA Carson, SJ Lee
PloS one 2011
Novel Role for SGK3 in Glucose Homeostasis Revealed in SGK3/Akt2 Double-Null Mice
LJ Yao, JA McCormick, J Wang, KY Yang, A Kidwai, GL Colussi, KM Boini, MJ Birnbaum, F Lang, MS German, D Pearce
Molecular Endocrinology 2011
Protective Role of Akt2 in Salmonella enterica Serovar Typhimurium-Induced Gastroenterocolitis
WW Kum, BC Lo, HB Yu, BB Finlay, BA McCormick
Infection and immunity 2011
Chamaejasmine Inactivates Akt To Trigger Apoptosis in Human HEp-2 Larynx Carcinoma Cells
Y Wang, Y Zhao, Y Liu, L Tian, D Jin
Molecules (Basel, Switzerland) 2011
Chiral kinase inhibitors.
Jiang JK, Shen M, Thomas CJ, Boxer MB
Current topics in medicinal chemistry 2011
Recent development of anticancer therapeutics targeting Akt.
Morrow JK, Du-Cuny L, Chen L, Meuillet EJ, Mash EA, Powis G, Zhang S
Recent Patents on Anti-Cancer Drug Discovery 2011

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