Abstract：
:Sustained activation of AMP-activated protein kinase (AMPK) induces apoptosis in several cell types. In pancreatic beta cells this occurs under glucose limitation, or in the presence of the pharmacological AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR). It is unknown whether Akt activation can counteract AMPK-mediated apoptosis, nor whether mTOR activation downstream of Akt mediates any survival signal in these conditions. We report that expression of a constitutively active form of Akt increases mTOR activity and prevents apoptosis upon AMPK activation. Akt-mediated survival was inhibited by rapamycin. Expression of a constitutively active form of the mTOR target ribosomal protein S6 kinase (S6K) or of translation factor eIF4E reduced apoptosis by glucose limitation, and co-expression of S6K and eIF4E protected beta cells to the same extent as active Akt. The protective effects of active Akt and S6K were associated with increased cellular protein synthesis activity. It is concluded that Akt stimulation of mTOR and subsequent activation of the targets by which mTOR affects protein translation are required and sufficient mechanisms for Akt-mediated survival of beta cells undergoing sustained AMPK activation.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Cai Y,Wang Q,Ling Z,Pipeleers D,McDermott P,Pende M,Heimberg H,Van de Casteele Mdoi
10.1016/j.bcp.2008.02.019subject
Has Abstractpub_date
2008-05-15 00:00:00pages
1981-93issue
10eissn
0006-2952issn
1873-2968pii
S0006-2952(08)00136-6journal_volume
75pub_type
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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