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.
