Abstract
Insulin stimulated translocation of the glucose transporter GLUT4 from the cytosol to the plasma membrane in a concentration (1 nM–1 μM)-dependent manner and increased glucose uptake in 3T3-L1 adipocytes. Insulin-induced GLUT4 translocation to the cell surface was prevented by the phosphoinositide 3 kinase (PI3K) inhibitor wortmannin, the 3-phosphoinositide-dependent protein kinase 1 (PDK1) inhibitor BX912 or the Akt1/2 inhibitor MK2206, and by knocking-down PI3K, PDK1 or Akt1/2. Insulin increased phosphorylation of Akt1/2 at Thr308/309 and Ser473/474, to activate Akt1/2, in the adipocytes. Insulin-induced phosphorylation of Akt1/2 was suppressed by wortmannin and knocking-down PI3K, while no significant inhibition of the phosphorylation was obtained with BX912 or knocking-down PDK1. In the cell-free Akt assay, PI3K phosphorylated Akt1 both at Thr308 and Ser473 and Akt2 at Ser474 alone. In contrast, PDK1 phosphorylates Akt1 at Thr308 and Akt2 at Thr309. The results of this study indicate that PI3K activates Akt1, independently of PDK1, and Akt2 by cooperating with PDK1 in the insulin signal transduction pathway linked to GLUT4 translocation.
Highlights
Akt is a serine/threonine protein kinase bearing multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration
We show here that insulin stimulates GLUT4 translocation to the cell surface and increases glucose uptake into 3T3-L1 adipocytes in an Akt1/2-dependent manner; phosphoinositide 3 kinase (PI3K) phosphorylates both Thr308 and Ser473 for Akt1 and Ser474 alone for Akt2; and PDK1 phosphorylates Thr308 for Akt1 and Akt2
Insulin stimulates GLUT4 translocation to the cell surface by activating insulin receptor, and when insulin receptor is inactivated, GLUT4 is rapidly removed from the plasma membrane into the cytosol and accumulated in intracellular organelles such as the trans-Golgi network, recycling endosome, and diverse tubulo-vesicular bodies (Bryant et al 2002, Rudich & Klip 2003, Watson et al 2004, Ishiki & Klip 2005)
Summary
Akt is a serine/threonine protein kinase bearing multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. Of the isoforms Akt exerts its anti-apoptotic action, thereby promoting cell survival (Song et al 2005). Akt is implicated in protein synthesis, responsible for skeletal muscle hypertrophy and tissue growth (Lai et al 2004). Accumulating evidence has indicated the involvement of Akt in many types of cancer (Cheung & Testa 2013). On the other hand, plays a pivotal role in glucose homeostasis. Akt stimulates translocation of the glucose transporter GLUT4, abundantly expressed in skeletal muscle and fat cells, to the cell surface, causing insulin-induced glucose uptake into cells (Garofalo et al 2003). Akt is preferentially expressed in the brain, but its role is not fully understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
