The use of glucose by the brain serves as an energy source and is requisite for the formation of several neurotransmitters. Aging may be associated with detrimental alterations in hepatic glucose production, cerebral glucose uptake, and related abnormalities on neuronal transmission. In contrast, endurance training is associated with enhanced hepatic gluconeogenic capacity. The proposed studies will examine the effects of endurance training and aging on the gluconeogenic response to distinct hormones and hormone concentrations in isolated hepatocytes. The extent of pyruvate kinase-L inhibition and alterations in the activity of phosphodiesterase and adenyl cyclase activation will be examined to elucidate the ability of training to attenuate the age related decline in hepatic gluconeogenesis. The overall aim is to delineate the training induced adaptations which enable the liver to enhance the response to hormone stimulation. Investigation of the specific enzyme regulatory site (pyruvate kinase-L) and molecular mechanisms involved in enzyme inhibition will lead to further understanding of mechanisms responsible for the enhanced gluconeogenic capacity of the liver following training.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15AG014565-01
Application #
2002469
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Finkelstein, David B
Project Start
1997-07-15
Project End
2000-06-30
Budget Start
1997-07-15
Budget End
2000-06-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Chapman University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Orange
State
CA
Country
United States
Zip Code
92866
Sumida, Ken D; Crandall, Suzanne C; Chadha, Puja L et al. (2005) Differential effects of alcohol upon gluconeogenesis from lactate in young and old hepatocytes. Exp Gerontol 40:324-9
Sumida, Ken D; Arimoto, Steven M; Catanzaro, Michael J et al. (2003) Effect of age and endurance training on the capacity for epinephrine-stimulated gluconeogenesis in rat hepatocytes. J Appl Physiol 95:712-9
Sumida, Ken D; Crandall, Suzanne C; Chadha, Puja L et al. (2002) Hepatic gluconeogenic capacity from various precursors in young versus old rats. Metabolism 51:876-80