Please use this identifier to cite or link to this item: https://doi.org/10.1152/ajpregu.00190.2009
Title: Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment
Authors: Bikman, B.T. 
Zheng, D.
Reed, M.A.
Hickner, R.C.
Houmard, J.A.
Dohm, G.L.
Keywords: 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside
Adenosine 5′-monophosphate-activated protein kinase
B kinase β
c-Jun amino-terminal kinase
Inhibitor of κ
Skeletal muscle
Issue Date: Jun-2010
Citation: Bikman, B.T., Zheng, D., Reed, M.A., Hickner, R.C., Houmard, J.A., Dohm, G.L. (2010-06). Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment. American Journal of Physiology - Regulatory Integrative and Comparative Physiology 298 (6) : R1692-R1699. ScholarBank@NUS Repository. https://doi.org/10.1152/ajpregu.00190.2009
Abstract: The molecular mechanisms of obesity-associated insulin resistance are becoming increasingly clear, and the effects of various lipid molecules, such as diacylglycerol and ceramide, on the insulin signal are being actively explored. To better understand the divergent response to lipid exposure between lean and obese, we incubated primary human muscle cells from lean [body mass index (BMI) >25 kg/m2] and morbidly obese (BMI >40 kg/m2) subjects with the saturated fatty acid palmitate. Additionally, given that AMPK-activating drugs are widely prescribed for their insulin-sensitizing effects, we sought to determine whether 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR)-stimulated AMPK activation could prevent or reverse the deleterious effects of lipid on insulin signaling. We found that a 1-h palmitate incubation in lean myotubes reduced (P < 0.05) insulin-stimulated phosphoprotein kinase B (Akt), Akt substrate 160 (AS160), and inhibitory factor κBα (IκBα) mass, all of which were prevented with AICAR inclusion. With a longer incubation, we observed that myotubes from morbidly obese individuals appear to be largely resistant to the detrimental effects of 16 h lipid exposure as was evident, in contrast to the lean, by the absence of a reduction in insulin-stimulated insulin receptor substrate (IRS)-1 Tyr phosphorylation, phospho-Akt, and phospho-AS160 (P < 0.05). Furthermore, 16 h lipid exposure significantly reduced IκBα levels and increased phosphorylation of c-Jun NH2-terminal kinase (JNK) and IRS1-Ser312 in lean myotubes only (P < 0.05). Despite a divergent response to lipid between lean and obese myotubes, AICAR inclusion improved insulin signaling in all myotubes. These findings suggest an important role for regular exercise in addition to offering a potential mechanism of action for oral AMPK-activating agents, such as thiazolidinediones and metformin. Copyright © 2010 the American Physiological Society.
Source Title: American Journal of Physiology - Regulatory Integrative and Comparative Physiology
URI: http://scholarbank.nus.edu.sg/handle/10635/124740
ISSN: 03636119
DOI: 10.1152/ajpregu.00190.2009
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