{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:33:33Z","timestamp":1790037213609,"version":"4.0.1"},"reference-count":49,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,10,1]]},"abstract":"<jats:p>PKB (protein kinase B), also known as Akt, is a key component of insulin signalling. Defects in PKB activation lead to insulin resistance and metabolic disorders, whereas PKB overactivation has been linked to tumour growth. Small-molecule PKB inhibitors have thus been developed for cancer treatment, but also represent useful tools to probe the roles of PKB in insulin action. In the present study, we examined the acute effects of two allosteric PKB inhibitors, MK-2206 and Akti 1\/2 (Akti) on PKB signalling in incubated rat soleus muscles. We also assessed the effects of the compounds on insulin-stimulated glucose uptake, glycogen and protein synthesis. MK-2206 dose-dependently inhibited insulin-stimulated PKB phosphorylation, PKB\u03b2 activity and phosphorylation of PKB downstream targets (including glycogen synthase kinase-3\u03b1\/\u03b2, proline-rich Akt substrate of 40\u00a0kDa and Akt substrate of 160\u00a0kDa). Insulin-stimulated glucose uptake, glycogen synthesis and glycogen synthase activity were also decreased by MK-2206\u00a0in a dose-dependent manner. Incubation with high doses of MK-2206 (10\u00a0\u03bcM) inhibited insulin-induced p70 ribosomal protein S6 kinase and 4E-BP1 (eukaryotic initiation factor 4E-binding protein-1) phosphorylation associated with increased eEF2 (eukaryotic elongation factor 2) phosphorylation. In contrast, Akti only modestly inhibited insulin-induced PKB and mTOR (mammalian target of rapamycin) signalling, with little or no effect on glucose uptake and protein synthesis. MK-2206, rather than Akti, would thus be the tool of choice for studying the role of PKB in insulin action in skeletal muscle. The results point to a key role for PKB in mediating insulin-stimulated glucose uptake, glycogen synthesis and protein synthesis in skeletal muscle.<\/jats:p>","DOI":"10.1042\/bj20120772","type":"journal-article","created":{"date-parts":[[2012,7,19]],"date-time":"2012-07-19T08:09:46Z","timestamp":1342685386000},"page":"137-147","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["A novel PKB\/Akt inhibitor, MK-2206, effectively inhibits insulin-stimulated glucose metabolism and protein synthesis in isolated rat skeletal muscle"],"prefix":"10.1042","volume":"447","author":[{"given":"Yu-Chiang","family":"Lai","sequence":"first","affiliation":[{"name":"Universit\u00e9 catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Universit\u00e9 catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxane","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Universit\u00e9 catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark\u00a0H.","family":"Rider","sequence":"additional","affiliation":[{"name":"Universit\u00e9 catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2012,9,12]]},"reference":[{"key":"2021112217333641100_B1","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.cell.2007.06.009","article-title":"AKT\/PKB signaling: navigating downstream","volume":"129","author":"Manning","year":"2007","journal-title":"Cell"},{"key":"2021112217333641100_B2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.ccr.2006.08.022","article-title":"Akt deficiency impairs normal cell proliferation and suppresses oncogenesis in a p53-independent and mTORC1-dependent manner","volume":"10","author":"Skeen","year":"2006","journal-title":"Cancer Cell"},{"key":"2021112217333641100_B3","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1101\/gad.1395006","article-title":"The deficiency of Akt1 is sufficient to suppress tumor development in Pten+\/\u2212 mice","volume":"20","author":"Chen","year":"2006","journal-title":"Genes Dev."},{"key":"2021112217333641100_B4","doi-asserted-by":"crossref","first-page":"e3065","DOI":"10.1371\/journal.pone.0003065","article-title":"Breast tumor cells with PI3K mutation or HER2 amplification are selectively addicted to Akt signaling","volume":"3","author":"She","year":"2008","journal-title":"PLoS ONE"},{"key":"2021112217333641100_B5","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/nrd2926","article-title":"Targeting the phosphoinositide 3-kinase pathway in cancer","volume":"8","author":"Liu","year":"2009","journal-title":"Nat. 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