Our earlier work defined and characterized the ability of glucagon, catecholamines, and insulin to regulate the increase in hepatic glucose production and the ability of insulin and catecholamines to control glucose utilization during exercise.
The aim of the studies in this proposal is to study the means by which substrate availability may influence hepatic and muscle carbohydrate metabolism during exercise, independent of changes in hormone levels. Specifically, we will study the means by which glucose, free fatty acids (FFAs), and O2 availability affect hepatic and muscle carbohydrate metabolism. Studies will be conducted during rest and treadmill exercise in overnight-fasted dogs in which hormone levels and neural outflow will be controlled using surgical (pancreatectomy, denervation, adrenalectomy) and pharmacological (somatostatin) methods. Hepatic glycogenolysis and gluconeogenesis and muscle glycogenolysis, glucose uptake, and glucose metabolism will be assessed using arteriovenous differences and tracer techniques. It is a goal of the proposed experiments to isolate the direct effects of changes in glucose, FFAs, and O2 availability from the effects which may be mediated by the endocrine and nervous systems. In the first set of experiments we will study the effects of altering glucose load on liver and muscle carbohydrate metabolism during exercise. The dynamics of insulin-independent glucose uptake and metabolism by the working muscle will be determined by varying the circulating glucose level in the presence of a fixed insulin concentration. In addition, the ability of a glucose load to modulate the exercise-induced rise in hepatic glycogenolysis and gluconeogenesis will be assessed. The second group of studies is designed to elucidate the impact of altering fat availability on hepatic and muscle carbohydrate metabolism during exercise in normal and insulin-deficient states. Moreover, we will determine the role of FFAs in mediating hormone action on glucose metabolism. In the third set of experiments the metabolic effects of the diminished O2 availability resulting from anemia will be determined.
The aim of these studies will be to elucidate the mechanism by which a decrease in O2 availability increases the reliance of the working muscle on carbohydrates as a fuel. An effort will be made in these studies to differentiate between the direct effects of a diminished O2 availability and those effects which are mediated by the endocrine system. These studies should further our understanding of the factors which regulate carbohydrate metabolism in the liver and working muscle under physiologic conditions and under pathologic conditions in which the circulating levels of glucose, FFA, and O2 may be altered.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK042488-05
Application #
2142322
Study Section
Metabolism Study Section (MET)
Project Start
1990-05-01
Project End
1995-04-30
Budget Start
1994-05-01
Budget End
1995-04-30
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Physiology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Zinker, B A; Wilson, R D; Wasserman, D H (1995) Interaction of decreased arterial PO2 and exercise on carbohydrate metabolism in the dog. Am J Physiol 269:E409-17
Zinker, B A; Wilson, R; Wasserman, D H (1995) Contribution of pancreatic hormone responses to the elevation in carbohydrate metabolism with reduced PaO2. Am J Physiol 268:E1174-83
Zinker, B A; Mohr, T; Kelly, P et al. (1994) Exercise-induced fall in insulin: mechanism of action at the liver and effects on muscle glucose metabolism. Am J Physiol 266:E683-9
O'Doherty, R M; Bracy, D P; Osawa, H et al. (1994) Rat skeletal muscle hexokinase II mRNA and activity are increased by a single bout of acute exercise. Am J Physiol 266:E171-8
Zinker, B A; Namdaran, K; Wilson, R et al. (1994) Acute adaptation of carbohydrate metabolism to decreased arterial PO2. Am J Physiol 266:E921-9
Berger, C M; Sharis, P J; Bracy, D P et al. (1994) Sensitivity of exercise-induced increase in hepatic glucose production to glucose supply and demand. Am J Physiol 267:E411-21
Wasserman, D H; Lacy, D B; Bracy, D P (1993) Relationship between arterial and portal vein immunoreactive glucagon during exercise. J Appl Physiol 75:724-9
Wasserman, D H; Johnson, J L; Bupp, J L et al. (1993) Regulation of gluconeogenesis during rest and exercise in the depancreatized dog. Am J Physiol 265:E51-60
Zinker, B A; Lacy, D B; Bracy, D et al. (1993) Regulation of glucose uptake and metabolism by working muscle. An in vivo analysis. Diabetes 42:956-65
Zinker, B A; Lacy, D B; Bracy, D P et al. (1993) Role of glucose and insulin loads to the exercising limb in increasing glucose uptake and metabolism. J Appl Physiol 74:2915-21

Showing the most recent 10 out of 16 publications