The time period following an acute bout of exercise is characterized by a greatly enhanced rate of glucose uptake and glycogen synthesis in skeletal muscle that may persist for several hours. The vast majority of glucose that is taken up by skeletal muscle is incorporated into glycogen, but little is known about the cellular signaling mechanisms that regulate this process. Therefore, the overall objective of my research project is to determine the molecular signaling mechanisms that regulate exercise-induced glycogen synthesis. Specifically, experiments are designed to study the roles of the muscle-specific, glycogen- and sarcoplasmic reticulum-associated protein phosphatase (PP 1 G) and the AMP-activated protein kinase (AMPK) in the regulation of glycogen synthesis following exercise, and the site-specific dephosphorylation of glycogen synthase that is associated with activation of the enzyme with muscle contractions. These studies will provide valuable information towards understanding the molecular basis of skeletal muscle glycogen metabolism. More importantly, this information may also be applied in the future towards understanding and treating the metabolic defects that are characteristic of chronic diseases such as type diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK059769-02
Application #
6517943
Study Section
Special Emphasis Panel (ZRG1-SSS-3 (02))
Program Officer
Hyde, James F
Project Start
2001-05-01
Project End
2003-03-28
Budget Start
2002-05-01
Budget End
2003-03-28
Support Year
2
Fiscal Year
2002
Total Cost
$40,986
Indirect Cost
Name
Joslin Diabetes Center
Department
Type
DUNS #
071723084
City
Boston
State
MA
Country
United States
Zip Code
02215
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
Aschenbach, William G; Sakamoto, Kei; Goodyear, Laurie J (2004) 5' adenosine monophosphate-activated protein kinase, metabolism and exercise. Sports Med 34:91-103
Omer, Abdulkadir; Duvivier-Kali, Valerie F; Aschenbach, William et al. (2004) Exercise induces hypoglycemia in rats with islet transplantation. Diabetes 53:360-5
Sakamoto, Kei; Aschenbach, William G; Hirshman, Michael F et al. (2003) Akt signaling in skeletal muscle: regulation by exercise and passive stretch. Am J Physiol Endocrinol Metab 285:E1081-8
Howlett, Kirsten F; Sakamoto, Kei; Hirshman, Michael F et al. (2002) Insulin signaling after exercise in insulin receptor substrate-2-deficient mice. Diabetes 51:479-83
Aschenbach, William G; Hirshman, Michael F; Fujii, Nobuharu et al. (2002) Effect of AICAR treatment on glycogen metabolism in skeletal muscle. Diabetes 51:567-73
Sakamoto, Kei; Hirshman, Michael F; Aschenbach, William G et al. (2002) Contraction regulation of Akt in rat skeletal muscle. J Biol Chem 277:11910-7
Aschenbach, W G; Suzuki, Y; Breeden, K et al. (2001) The muscle-specific protein phosphatase PP1G/R(GL)(G(M))is essential for activation of glycogen synthase by exercise. J Biol Chem 276:39959-67