This research project is designed to advance the understanding of the role of hormones as mediators of the metabolic responses to injury. It is hoped that the knowledge gained from these studies may contribute to the development of more effective therapeutic strategies for the critically ill and injured patient. Specifically the goal of the project is to determine how insulin may affect the combined catabolic effects of cortisol, glucagon, and epinephrine. The hypotheses to be tested are: 1) Simultaneous physiologic elevations of the concentrations of the three hormones cortisol, glucagon, and epinephrine can accelerate net skeletal muscle proteolysis. 2) This catabolic hormonal effect may be significantly attenuated by a concurrent increase in serum insulin concentration. 3) This modifying effect of insulin may itself be reduced if insulin concentration does not rise until after the catabolic hormonal effects have become established. The studies would be performed in normal, healthy, human male volunteer subjects. Sustained elevations of the concentrations of the catabolic hormones would be achieved by the infusion of a combined mixture of hydrocortisone, glucagon, and epinephrine. Insulin concentration would be controlled by both separate and combined infusions of insulin and a somatostatin analog. several metabolic determinations would be made including oxygen consumption and carbon dioxide production; forearm blood flow and exchange of glucose, lactate, and amino acids; nitrogen balance; excretion of 3-methylhistidine; intracellular skeletal muscle amino acid concentration; concentration of free fatty acids and ketone bodies; and hormone concentration. The studies would attempt to define the effect of the catabolic hormones alone on these several metabolic parameters, and to delineate how insulin may modify the catabolic hormonal effects.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM041961-01
Application #
3300465
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1988-08-01
Project End
1992-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130