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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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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: 6 9 9 9 19 14 19 11 22 10 24 23 24 27 25 18 20 14 7 8 7 6 2 333
Citation information
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Citations to this article in year 2020 (14)

Title and authors Publication Year
Regulation of basal expression of hepatic PEPCK and G6Pase by AKT2
L He, Y Li, N Zeng, BL Stiles
Biochemical Journal 2020
Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence
Y Tan, Z Zhang, C Zheng, KA Wintergerst, BB Keller, L Cai
Nature Reviews Cardiology 2020
AKT2 deficiency impairs formation of the BCR signalosome
Z Du, D Yang, Y Zhang, X Xuan, H Li, L Hu, C Ruan, L Li, A Chen, L Deng, Y Chen, J Xie, LS Westerberg, L Huang, C Liu
Cell Communication and Signaling 2020
Regulation of Hematopoietic Stem Cell Fate and Malignancy
HJ Cho, J Lee, SR Yoon, HG Lee, H Jung
International journal of molecular sciences 2020
Social Support and User Characteristics in Online Diabetes Communities: An In-Depth Survey of a Large-Scale Chinese Population
D Liang, G Fan
International journal of environmental research and public health 2020
The p21‐activated kinase 2 (PAK2), but not PAK1, regulates contraction‐stimulated skeletal muscle glucose transport
LL Møller, IL Nielsen, JR Knudsen, NR Andersen, TE Jensen, L Sylow, EA Richter
Physiological Reports 2020
PKBβ/AKT2 deficiency impacts brain mTOR signaling, prefrontal cortical physiology, hippocampal plasticity and select murine behaviors
S Palumbo, C Paterson, F Yang, VL Hood, AJ Law
Molecular Psychiatry 2020
Metoprolol alleviates arginine vasopressin-induced cardiomyocyte hypertrophy by upregulating the AKT1–SERCA2 cascade in H9C2 cells
J Zhao, Y Lei, Y Yang, H Gao, Z Gai, X Li
Cell & Bioscience 2020
Akt isoform-specific effects on thyroid cancer development and progression in a murine thyroid cancer model
M Saji, CS Kim, C Wang, X Zhang, T Khanal, K Coombes, KL Perle, SY Cheng, PN Tsichlis, MD Ringel
Scientific Reports 2020
Quantitative Phosphoproteomic Analysis Reveals the Regulatory Networks of Elovl6 on Lipid and Glucose Metabolism in Zebrafish
X Wang, S Sun, X Cao, J Gao
International journal of molecular sciences 2020
The Role of Akt2 in the Protective Effect of Fenofibrate against Diabetic Nephropathy.
Cheng Y, Zhang X, Ma F, Sun W, Wang W, Yu J, Shi Y, Cai L, Xu Z
International journal of biological sciences 2020
Putative functional variants of PI3K/AKT/mTOR pathway are associated with knee osteoarthritis susceptibility.
Wang K, Chu M, Wang F, Zhao Y, Chen H, Dai X
Journal of Clinical Laboratory Analysis 2020
Alternative AKT2 splicing produces protein lacking the hydrophobic motif regulatory region.
Plotz G, Lopez-Garcia LA, Brieger A, Zeuzem S, Biondi RM
PloS one 2020
Acer tegmentosum Maxim Inhibits Adipogenesis in 3t3-l1 Adipocytes and Attenuates Lipid Accumulation in Obese Rats Fed a High-Fat Diet.
Cho HH, Lee SJ, Kim SH, Jang SH, Won C, Kim HD, Kim TH, Cho JH
Nutrients 2020

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