Specifying """"""""good"""""""" nutrition or the appropriate level of nutrients in either the clinical setting or in healthy normal individuals is dependent upon our knowledge of the basic biochemistry and metabolism of the nutrients being administered. Included in this nutritional database must also be knowledge of how the body regulates flows and stores of the critical elements of energy and protein metabolism in health and disease. This understanding should be mandatory before new enteral or parenteral feeding solution are proposed with novel combinations of nutrients. Yet this advice is often ignored. The long term goals of this proposal continue to be studies of amino acid and protein metabolism in humans 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 of how dietary amino acids are utilized by the splanchnic bed in the fed state. These studies will address the importance of the hormones insulin and glucagon versus substrate signals in mediating splanchnic bed utilization of amino acids. (2) To define the role of glucagon in disposal of amino acids coming from muscle and other peripheral tissues, 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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