Salt, I., Connell, J., and Gould, G. (2000) 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes. Diabetes, 49 (10). pp. 1649-1656. ISSN 0012-1797 (doi:10.2337/diabetes.49.10.1649)
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Incubation of skeletal muscle with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a compound that activates 5'-AMP-activated protein kinase (AMPK), has been demonstrated to stimulate glucose transport and GLUT4 translocation to the plasma membrane. In this study, we characterized the AMPK cascade in 3T3-L1 adipocytes and the response of glucose transport to incubation with AICAR, Both isoforms of the catalytic alpha-subunit of AMPK are expressed in 3T3-L1 adipocytes, in which AICAR stimulated AMPK( activity in a time- and dose-dependent fashion. AICAR stimulated 8-deoxy-D-glucose transport twofold and reduced insulin-stimulated uptake to 62% of the control transport rate dose-dependently, closely correlating with the activation of AMPK. AICAR also inhibited insulin-stimulated GLUT4 translocation, assessed using the plasma membrane lawn assay. The effects of AICAR on insulin-stimulated glucose transport are not mediated by either adenosine receptors or nitric oxide synthase and are mediated downstream of phosphatidylinositol 3'-kinase stimulation. We propose that in contrast to skeletal muscle, in which AMPK stimulation promotes glucose transport to provide ATP as a fuel, AMPK stimulation inhibits insulin-stimulated glucose transport in adipocytes, inhibiting triacylglycerol synthesis, to conserve ATP under conditions of cellular stress. Investigation of the mode of action of AICAR and AMPK may, therefore, give insight into the mechanism of insulin action.
|Glasgow Author(s) Enlighten ID:||Gould, Prof Gwyn and Salt, Dr Ian and Connell, Prof John|
|Authors:||Salt, I., Connell, J., and Gould, G.|
|College/School:||College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology|
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences