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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: 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 2006 (8)

Title and authors Publication Year
Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3
HJ Koh, DE Arnolds, N Fujii, TT Tran, MJ Rogers, N Jessen, Y Li, CW Liew, RC Ho, MF Hirshman, RN Kulkarni, CR Kahn, LJ Goodyear
Molecular and cellular biology 2006
Potential impact of carbohydrate and fat intake on pathological left ventricular hypertrophy
N Sharma, IC Okere, MK Duda, DJ Chess, KM O'Shea, WC Stanley
Cardiovascular Research 2006
An RNA interference-based screen identifies MAP4K4/NIK as a negative regulator of PPARgamma, adipogenesis, and insulin-responsive hexose transport
X Tang, A Guilherme, A Chakladar, AM Powelka, S Konda, JV Virbasius, SM Nicoloro, J Straubhaar, MP Czech
Proceedings of the National Academy of Sciences 2006
AKT phosphorylation is essential for insulin-induced relaxation of rat vascular smooth muscle cells
JH Lee, L Ragolia
American journal of physiology. Cell physiology 2006
Only Akt1 Is Required for Proliferation, while Akt2 Promotes Cell Cycle Exit through p21 Binding
L Héron-Milhavet, C Franckhauser, V Rana, C Berthenet, D Fisher, BA Hemmings, A Fernandez, NJ Lamb
Molecular and cellular biology 2006
Akt2 Regulates Cardiac Metabolism and Cardiomyocyte Survival
B DeBosch, N Sambandam, C Weinheimer, M Courtois, AJ Muslin
The Journal of biological chemistry 2006
Life with a Single Isoform of Akt: Mice Lacking Akt2 and Akt3 Are Viable but Display Impaired Glucose Homeostasis and Growth Deficiencies
B Dummler, O Tschopp, D Hynx, ZZ Yang, S Dirnhofer, BA Hemmings
Molecular and cellular biology 2006
Akt1 in Endothelial Cell and Angiogenesis
Somanath PR, Razorenova OV, Chen J, Byzova TV
Cell cycle (Georgetown, Tex.) 2006

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