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Molecular mechanisms underlying AMPK‐induced inhibition of glucose uptake in primary rat adipocytes
Author(s) -
Ceddia Rolando B.,
Perry Robert,
Gaidhu Mandeep P.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.659.3
Subject(s) - ampk , glucose uptake , medicine , phosphorylation , endocrinology , chemistry , protein kinase a , protein kinase b , amp activated protein kinase , glucose transporter , insulin , microbiology and biotechnology , biology , biochemistry
This study investigated the molecular mechanisms by which AMP‐kinase (AMPK) activation inhibits basal and insulin‐stimulated glucose uptake in primary adipocytes. Rat epididymal adipocytes were exposed to AICAR for 1h. Subsequently, glucose uptake and the phosphorylation states of AMPK, ACC, Akt, and the Akt substrate of 160kDa (AS160) were determined in primary adipocytes either expressing LacZ (control) or a kinase dead AMPKα1 mutant (KD‐AMPKα1). AICAR increased AMPK and ACC phopshorylation, without affecting basal and insulin‐stimulated Akt phosphorylation. However, AMPK activation suppressed AS160 phosphorylation by 80% and 50% and glucose uptake by 35% and 50% under basal and insulin‐stimulated conditions, respectively. Expression of the KD‐AMPKα1 mutant fully prevented the suppression of AS160 phosphorylation as well as the inhibitory effect of AICAR‐induced AMPK activation on basal and insulin‐stimulated glucose uptake. This study provides novel evidence that suppression of AS160 phosphorylation by AICAR‐induced AMPK activation leads to inhibition of basal and insulin‐stimulated glucose uptake in primary rat adipocytes. Disruption of AMPKα1 signaling fully prevented these effects, indicating that insulin‐signaling steps that are common to white adipose tissue and skeletal muscle regulation of glucose uptake are distinctly affected by AMPK activation in these tissues.