Specifying good nutrition or the appropriate level of nutrients is dependent upon our knowledge of how the body regulates flows and stores of the critical elements of energy and protein metabolism in health and disease. The long-term goals of this proposal are to elucidate how the body regulates amino acids and protein in the body, how it handles dietary intake, and how other nutrients (e.g. carbohydrate and fat) interact with them. Our approach has been to administer stable isotopically labeled amino acid tracers to determine amino acid and protein kinetics in healthy individuals. There are 2 arms to these studies: (a) determination of amino acid metabolism in normal individuals to define normal physiology and (b) to understand amino acid metabolism in states of pathophysiology (e.g. injury or metabolic disease) by mimicking in healthy individuals through administration of one or more hormones or other mediators the particular aspect of disease to be studied. This proposal has 3 aims: (1) To define how dietary amino acids are utilized by the splanchnic bed in the fed state, including the role of insulin and glucagon in mediating splanchnic bed utilization of amino acids. (2) To define the role of glucagon in disposal of amino acids, particularly glutamine and alanine, for production of glucose. (3) To define whether therapeutic analogues of cortisol used for treatment of inflammation and immune suppression produce similar increases in resting energy expenditure as we have defined for cortisol.
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