Disease relevance of Akt2

• Insulin-stimulated insulin receptor substrate 2 and Akt-2 phosphorylation were significantly blunted in IUGR rats [1].

High impact information on Akt2

• In addition to increasing phosphorylation, contraction in situ significantly increased the activity of all three Akt isoforms (Akt1 > Akt2 > Akt3) with maximal activation occurring at 2.5 min and returning to base line with 15 min of contraction [2].
• Insulin action on Akt2 and p70S6K were not impaired, whereas activation of protein kinase C lambda/zeta activity was reduced 47% [3].
• These findings suggest that PI3K-dependent effects on glucose transport in adipocytes are not mediated primarily by Akt2 [4].
• To determine whether impaired Akt (protein kinase B or rac) activation contributes to insulin resistance in vivo, we examined the expression, phosphorylation, and kinase activities of Akt1 and Akt2 isoforms in insulin target tissues of insulin-resistant obese Zucker rats [4].
• In lean rats, insulin (10 U/kg i.v. x 2.5 min) stimulated Akt1 activity 6.2-, 8.8-, and 4.4-fold and Akt2 activity 5.4-, 9.3-, and 1.8-fold in muscle, liver, and adipose tissue, respectively [4].

Anatomical context of Akt2

• Akt1 and Akt2 activations by insulin have a similar time course and are maximal by 2.5 min in adipocytes of both lean and obese rats [4].
• Insulin-stimulated Akt2 activity decreased 29% in muscle and 37% in liver but increased 24% in adipose tissue [4].
• High fat feeding did not alter total skeletal muscle Akt2, aPKC zeta or aPKC lambda protein concentration [5].
• Insulin-stimulated plasma membrane association and activation of Akt2, aPKC zeta and aPKC lambda in high fat fed rodent skeletal muscle [5].
• Activities of Akt1, Akt2, and Akt3 kinases and glucose uptake in hindlimb muscles of the rat in vivo were investigated [6].

Associations of Akt2 with chemical compounds

• In contrast, the exercised calf muscles exhibited an increase in Akt1 kinase activity at 5, 15, and 25 min of exercise but no change in activities of Akt2 and Akt3 isoforms, and the 2-deoxyglucose uptake by calf muscles exercised for 25 min was 11-fold higher compared with muscles of resting rats [6].
• The distribution of Akt-2 in resting adipocytes was found to substantially overlap with that of Glut4 when light microsomes were subfractionated by a sucrose velocity gradient indicating possible co-localization [7].
• In contrast, chronic aerobic exercise increased insulin-stimulated phosphatidylinositol 3-kinase, Akt 2 kinase and aPKC-zeta/lambda kinase activities, as well as c-Cbl tyrosine phosphorylation, in a fibre type specific response to aerobic training [8].

Physical interactions of Akt2

• Akt-2 binds to Glut4-containing vesicles and phosphorylates their component proteins in response to insulin [9].

Other interactions of Akt2

• Maximal insulin-stimulated (100 nmol/l) glucose transport was reduced 70% in isolated adipocytes, with a rightward shift in the insulin dose response for transport and for Akt1 stimulation but normal sensitivity for Akt2 [4].
• Akt-2 is found to be recruited to Glut4-containing vesicles in response to insulin [9].
• O-GlcNAc modification on IRS-1 and Akt2 by PUGNAc inhibits their phosphorylation and induces insulin resistance in rat primary adipocytes [10].
• These vesicles also containend Rab4 and Akt-2, the latter being only associated after insulin stimulation [11].

Analytical, diagnostic and therapeutic context of Akt2

• By means of MonoQ chromatography and Western blot analysis, vesicle-associated protein kinase is identified as Akt-2, a lipid-binding protein kinase involved in insulin signaling [9].

References