Physical exercise has been shown to have favorable effects on the development, management, and treatment of many metabolic diseases, including type 2 diabetes. A single bout of exercise can elicit significant cellular effects resulting in changes in glucose transport, glycogen metabolism, lipid metabolism, protein synthesis, and gene transcription. Furthermore, chronic exercise can lead to long-term adaptations (e.g. hypertrophy). The signaling mechanisms by which exercise elicits these effects remains poorly understood. Considering the marked activation of mitogen-activated protein kinases (MAPK) by exercise in skeletal muscle, it seems reasonable to implicate this family of signaling molecules as putative regulators of at least some of these biological responses. The overall goal of this project is to elucidate the signaling mechanisms and biological processes regulated by exercise- and contraction-mediated p38 MAPK activation in skeletal muscle. Particularly, my goal is to identify the isoform-specific activation of p38 MAPK in contracting skeletal muscle. The 5'-AMP-activated protein kinase (AMPK) is known to mediate contraction-induced glucose transport in skeletal muscle. My goal is also to determine whether p38 is a downstream target of AMPK, and contributes to increases in contraction-induced skeletal muscle glucose transport.
