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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 2008 (14)

Title and authors Publication Year
Regulation of pancreas plasticity and malignant transformation by Akt signaling
L Elghazi, AJ Weiss, DJ Barker, J Callaghan, L Staloch, EP Sandgren, M Gannon, VN Adsay, E Bernal-Mizrachi
Gastroenterology 2008
β-cell failure as a complication of diabetes
KJ Chang-Chen, R Mullur, E Bernal-Mizrachi
Reviews in Endocrine and Metabolic Disorders 2008
Mechanisms of Disease: using genetically altered mice to study concepts of type 2 diabetes
D Leroith, D Accili
Nature Clinical Practice Endocrinology & Metabolism 2008
Minireview: Obesity and LipOdystrophy—Where Do the Circles Intersect?
FF Chehab
Endocrinology 2008
Genetic modelling of the PTEN/AKT pathway in cancer research
O Renner, C Blanco-Aparicio, A Carnero
Clinical and Translational Oncology 2008
Distinct roles of the three Akt isoforms in lactogenic differentiation and involution
IG Maroulakou, W Oemler, SP Naber, I Klebba, C Kuperwasser, PN Tsichlis
Journal of Cellular Physiology 2008
Impaired insulin-mediated vasorelaxation in diabetic Goto-Kakizaki rats is caused by impaired Akt phosphorylation
JH Lee, T Palaia, L Ragolia
American journal of physiology. Cell physiology 2008
Mutation of the PDK1 PH Domain Inhibits Protein Kinase B/Akt, Leading to Small Size and Insulin Resistance
JR Bayascas, S Wullschleger, K Sakamoto, JM García-Martínez, C Clacher, D Komander, DM van Aalten, KM Boini, F Lang, C Lipina, L Logie, C Sutherland, JA Chudek, JA van Diepen, PJ Voshol, JM Lucocq, DR Alessi
Molecular and cellular biology 2008
Genetic and Molecular Basis of QTL of Diabetes in Mouse: Genes and Polymorphisms
P Gao, Y Jiao, Q Xiong, CY Wang, I Gerling, W Gu
Current genomics 2008
Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic
K Sakamoto, GD Holman
American journal of physiology. Endocrinology and metabolism 2008
Akt1 is necessary for the vascular maturation and angiogenesis during cutaneous wound healing
PR Somanath, J Chen, TV Byzova
Angiogenesis 2008
IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival
JA Wofford, HL Wieman, SR Jacobs, Y Zhao, JC Rathmell
Blood 2008
Age-related changes of calcineurin and Akt1/protein kinase Bα (Akt1/PKBα) immunoreactivity in the mouse hippocampal CA1 sector: an immunohistochemical study
R Eto, M Abe, N Hayakawa, H Kato, T Araki
Metabolic Brain Disease 2008
In Vivo Analysis of Protein Kinase B (PKB)/Akt Regulation in DNA-PKcs-null Mice Reveals a Role for PKB/Akt in DNA Damage Response and Tumorigenesis
B Surucu, L Bozulic, D Hynx, A Parcellier, BA Hemmings
The Journal of biological chemistry 2008

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