The broad objective of this project is to investigate the effect of burn injury on the endocrine regulation of carbohydrate metabolism and specifically the sensitivity of the organism to insulin. Burn injury is followed by the development of insulin resistance, the exact cause of which is not understood. The aims of this study are (1) to define the time course of insulin resistance after experimental burn injury, (2) to verify that the resistance is due to burn injury and not due to the nutritional status, (3) to determine the time course of changes after burn injury in serum concentrations of anti-insulin substances (free fatty acids, glucagon, glucocorticoids, growth hormone), (4) to evaluate the effect of ganglionic blockade or fall in post-burn serum glucocorticoid levels on the development of insulin resistance, and (5) to determine whether post-burn insulin resistance is due to a tissue defect. The mode of post-burn insulin resistance in the rat, currently used in our laboratory, will be employed and both in vivo and in vitro experiments will be conducted to analyze the relative importance of various anti-insulin factors in plasma and in the tissues for the development of post-burn insulin resistance. It is anticipated that the new information will aid in putting the largely empirical treatment of burned patients on a more physiological basis and that it will ultimately contribute to the definition of new concepts which will improve the management of burn patients and accelerate their recovery.