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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 2018 (11)

Title and authors Publication Year
Resolving the Paradox of Hepatic Insulin Resistance
D Santoleri, PM Titchenell
CMGH Cellular and Molecular Gastroenterology and Hepatology 2018
Differential effects of dietary flavonoids on adipogenesis
M Khalilpourfarshbafi, K Gholami, DD Murugan, MZ Sattar, NA Abdullah
European Journal of Nutrition 2018
Double knockout of Akt2 and AMPK predisposes cardiac aging without affecting lifespan: Role of autophagy and mitophagy
S Wang, MR Kandadi, J Ren
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2018
Connexin43 and zonula occludens-1 are targets of Akt in cardiomyocytes that correlate with cardiac contractile dysfunction in Akt deficient hearts
S Ock, WS Lee, HM Kim, KS Park, YK Kim, H Kook, WJ Park, TJ Lee, ED Abel, J Kim
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2018
Cyclical expression of GDNF is required for spermatogonial stem cell homeostasis
M Sharma, RE Braun
Development (Cambridge, England) 2018
Lack of serum- and glucocorticoid-inducible kinase 3 leads to podocyte dysfunction
LQ Peng, H Zhao, S Liu, YP Yuan, CY Yuan, MJ Mwamunyi, D Pearce, LJ Yao
The FASEB Journal 2018
Role of Akt Isoforms Controlling Cancer Stem Cell Survival, Phenotype and Self-Renewal
S Rivas, C Gómez-Oro, I Antón, F Wandosell
Biomedicines 2018
Dual Effects of Metformin on Adipogenic Differentiation of 3T3-L1 Preadipocyte in AMPK-Dependent and Independent Manners
D Chen, Y Wang, K Wu, X Wang
International journal of molecular sciences 2018
Akt2 (Protein Kinase B Beta) Stabilizes ATP7A, a Copper Transporter for Extracellular Superoxide Dismutase, in Vascular Smooth MuscleHighlights: Novel Mechanism to Limit Endothelial Dysfunction in Type 2 Diabetes Mellitus
V Sudhahar, MN Okur, Z Bagi, JP OBryan, N Hay, A Makino, VS Patel, SA Phillips, D Stepp, M Ushio-Fukai, T Fukai
Arteriosclerosis, thrombosis, and vascular biology 2018
Akt2 causes TGFβ-induced deptor downregulation facilitating mTOR to drive podocyte hypertrophy and matrix protein expression
F Das, N Ghosh-Choudhury, DY Lee, Y Gorin, BS Kasinath, GG Choudhury, JC Dussaule
PloS one 2018
Phosphorylated Akt1 expression is associated with poor prognosis in cutaneous, oral and sinonasal melanomas
C Soares, TM de Lima Morais, R Carlos, FV Mariano, A Altemani, MG de Carvalho, MB Corrêa, RR dos Reis, LS Amorim, OP de Almeida, J Jorge
Oncotarget 2018

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