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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AR049662-02
Application #
6719082
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Nuckolls, Glen H
Project Start
2003-03-01
Project End
2004-12-31
Budget Start
2004-03-01
Budget End
2004-12-31
Support Year
2
Fiscal Year
2004
Total Cost
$40,329
Indirect Cost
Name
Joslin Diabetes Center
Department
Type
DUNS #
071723084
City
Boston
State
MA
Country
United States
Zip Code
02215
Fujii, Nobuharu; Ho, Richard C; Manabe, Yasuko et al. (2008) Ablation of AMP-activated protein kinase alpha2 activity exacerbates insulin resistance induced by high-fat feeding of mice. Diabetes 57:2958-66
Aschenbach, William G; Ho, Richard C; Sakamoto, Kei et al. (2006) Regulation of dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3beta signaling pathway. Am J Physiol Endocrinol Metab 291:E152-8
Fujii, Nobuharu; Hirshman, Michael F; Kane, Erin M et al. (2005) AMP-activated protein kinase alpha2 activity is not essential for contraction- and hyperosmolarity-induced glucose transport in skeletal muscle. J Biol Chem 280:39033-41
Ho, Richard C; Hirshman, Michael F; Li, Yangfeng et al. (2005) Regulation of IkappaB kinase and NF-kappaB in contracting adult rat skeletal muscle. Am J Physiol Cell Physiol 289:C794-801
Ho, Richard C; Alcazar, Oscar; Fujii, Nobuharu et al. (2004) p38gamma MAPK regulation of glucose transporter expression and glucose uptake in L6 myotubes and mouse skeletal muscle. Am J Physiol Regul Integr Comp Physiol 286:R342-9