Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Disruption of AMPKalpha1 signaling prevents AICAR-induced inhibition of AS160/TBC1D4 phosphorylation and glucose uptake in primary rat adipocytes.

Authors: Gaidhu, MP  Perry, RL  Noor, F  Ceddia, RB 
Citation: Gaidhu MP, etal., Mol Endocrinol. 2010 Jul;24(7):1434-40. Epub 2010 May 25.
Pubmed: (View Article at PubMed) PMID:20501641
DOI: Full-text: DOI:10.1210/me.2009-0502

The aim of this study was to investigate 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 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) for 1 h. Subsequently, basal and insulin-stimulated glucose uptake and the phosphorylation of AMPK, acetyl-CoA carboxylase, Akt, and the Akt substrate of 160 kDa (AS160/TBC1D4) were determined. In order to investigate whether these effects of AICAR were mediated by AMPK activation, these parameters were also assessed in adipocytes either expressing LacZ (control) or a kinase-dead AMPKalpha1 mutant. AICAR increased AMPK activation without affecting basal and insulin-stimulated Akt1/2 phosphorylation on Thr(308) and Ser(473) residues. However, AMPK activation suppressed the phosphorylation of AS160/TBC1D4 and its interaction with the 14-3-3 signal transduction-regulatory protein, which was accompanied by significant reductions in plasma membrane glucose transporter 4 content and glucose uptake under basal and insulin-stimulated conditions. Phosphorylation of Akt substrates glycogen synthase kinase 3alpha and -beta were unaltered by AICAR, indicating that the AMPK-regulatory effects were specific to the AS160/TBC1D4 signaling pathway. Expression of the kinase-dead AMPKalpha1 mutant fully prevented the suppression of AS160/TBC1D4 phosphorylation, plasma membrane glucose transporter 4 content, and the inhibitory effect of AICAR-induced AMPK activation on basal and insulin-stimulated glucose uptake. This study is the first to provide evidence that disruption of AMPKalpha1 signaling prevents the suppressive effects of AMPK activation on AS160/TBC1D4 phosphorylation and glucose uptake, 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.

Annotation

Gene Ontology Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 6484547
Created: 2012-06-22
Species: All species
Last Modified: 2012-06-22
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.