Ataxia telangiectasia mutated (ATM) influences AICAR‐stimulated glucose transport

Abstract

Literature reports suggest that ATM can activate the AMP‐activated protein kinase (AMPK), a protein that can stimulate glucose transport in skeletal muscle. We hypothesized that AICAR, an AMPK activator, would increase AMPK phosphorylation and glucose transport in an ATM‐dependent manner. Extensor digitorum longus (EDL) muscles from wild‐type mice were exposed to 2 mM AICAR for one hour in the absence or presence of KU55933, a specific inhibitor of ATM. In separate procedures, wild‐type and ATM‐deficient (ATM−/−) EDL were exposed to AICAR. AICAR‐stimulated glucose transport was prevented by the ATM inhibitor despite no effect on AICAR‐stimulated phosphorylation of AMPK. AICAR increased glucose transport in EDL from wild‐type but not ATM−/− mice despite normal AICAR‐stimulated phosphorylation of AMPK in ATM−/− mice. Preliminary work (n=2–3) suggests that AICAR‐stimulated phosphorylation of TBC1D1 at S237 is prevented by inhibition of ATM. Our results suggest that ATM plays a role in AICAR‐stimulated glucose transport. However, contrary to our original hypothesis, ATM's influence occurs independent of AMPK phosphorylation, perhaps at the level of TBC1D1. Supported by USPHS award R15DK080437.