Akt1/PKBα Is Required for Normal Growth but Dispensable for Maintenance of Glucose Homeostasis in Mice*
By Han Cho, J. L. Thorvaldsen, Q. Chu, Fei-xue Feng, M. Birnbaum. Journal of Biological Chemistry, 2001
897 citations recorded by the source corpus.
The serine-threonine kinase Akt, also known as protein kinase B (PKB), is an important effector for phosphatidylinositol 3-kinase signaling initiated by numerous growth factors and hormones. Akt2/PKBβ, one of three known mammalian isoforms of Akt/PKB, has been demonstrated recently to be required for at least some of the metabolic actions of insulin (Cho, H., Mu, J., Kim, J. K., Thorvaldsen, J. L., Chu, Q., Crenshaw, E. B., Kaestner, K. H., Bartolomei, M. S., Shulman, G. I., and Birnbaum, M. J. (2001) Science292, 1728–1731). Here we show that mice deficient in another closely related isoform of the kinase, Akt1/PKBα, display a conspicuous impairment in organismal growth. Akt1 −/− mice demonstrated defects in both fetal and postnatal growth, and these persisted into adulthood. However, in striking contrast to Akt2/PKBβ null mice, Akt1/PKBα-deficient mice are normal with regard to glucose tolerance and insulin-stimulated disposal of blood glucose. Thus, the characterization of the Akt1 knockout mice and its comparison to the previously reported Akt2 deficiency phenotype reveals the non-redundant functions of Akt1 andAkt2 genes with respect to organismal growth and insulin-regulated glucose metabolism.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/bb34988d4e467679df241953089dac6a60bcedfe
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Citations in the corpus
- Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. (2003, background): “In addition, the effect of Akt on the translocation of the GENES & DEVELOPMENT 1361 glucose transporter, GLUT4 (Cong et al. 1997), contributes to adipocyte function.”
- Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta. (2003, background): “Both Akt1-null and Akt2-null mice are viable, but Akt1-deficient mice exhibit a growth deficiency and normal glucose metabolism (23, 24), whereas Akt2-deficient mice exhibit insulin resistance and mild diabetes with no apparent difference in size (25).”
- PI3K/Akt: getting it right matters (2008, background): “…specific phenotypes: Akt1( / ) mice show placental hypotrophy, accompanied by retardation of growth and reduction of body weight (Chen et al., 2001; Cho et al., 2001b); Akt2( / ) mice become hyperinsulemic and hyperglycemic (Cho et al., 2001a); and Akt3( / ) mice exhibit reduced brain sizes…”
- Protein kinase cascades in the regulation of cardiac hypertrophy. (2005, background): “than wild-type littermates and have a proportional reduction in size of all somatic tissues, including the heart (31).”
- From mice to men: insights into the insulin resistance syndromes. (2006, background): “Knockout of Akt1, the ubiquitously expressed isoform of Akt1, produces a global defect in growth but essentially no alterations in glucose homeostasis (110).”
- Molecular distinction between physiological and pathological cardiac hypertrophy: experimental findings and therapeutic strategies. (2010, background): “In mammals, Akt1 null mice had a 20% reduction in body weight (Cho et al., 2001).”