Acute heat treatment improves insulin-stimulated glucose uptake in aged skeletal muscle

Abstract

Aging is associated with insulin resistance and decreased insulin-stimulated glucose uptake into skeletal muscle. Although the mechanisms underlying age-related insulin resistance are not clearly defined, impaired defense against inflammation and tissue oxidative stress are likely causes. Heat shock proteins (HSPs) have been shown to protect tissue from oxidative stress and inhibit the activation of stress kinases such as JNK, known to interfere with the insulin signaling pathway. While the induction of HSPs via chronic heat treatment has been shown to protect skeletal muscle from obesity-related insulin resistance, the ability of heat treatment to improve insulin action in aged skeletal muscle is not known. In the present study, one bout of in vivo heat treatment applied to 24-mo-old Fischer 344 rats improved insulin-stimulated glucose uptake after 24 h in slow-twitch soleus muscles. In vitro heat treatment applied to young (3-mo-old) and aged (24-mo-old) soleus muscles increased expression of HSP72 and inhibited anisomycin-induced activation of JNK. In contrast, heat treatment had no effect on p38 MAPK, a MAPK strongly activated with anisomycin. Prior inhibition of HSP72 transcription with the pharmacological inhibitor KNK437 eliminated the ability of heat treatment to blunt JNK activation. This suggests that the ability of heat treatment to inhibit JNK activation in skeletal muscle is dependent on increased HSP72 expression. In conclusion, an acute bout of heat treatment can increase insulin-stimulated glucose uptake in aged skeletal muscle, with the underlying mechanism likely to be HSP72-mediated JNK inhibition.