The long-range objectives of this research proposal are to define in normal and obese man the roles of insulin, glucagon and glucose concentration on splanchnic and forearm metabolism. Somatostatin is administered which inhibits release of insulin and of glucagon. Euglycemia is maintained by variable infusion of glucose. It is then possible to infuse insulin and glucagon, singly or together, to dissect apart their individual roles. Our studies to date have shown dynamic interaction of basal insulin and glucagon in control of net splanchnic glucose output (NSGO). We plan to establish 1) effects of glucagon at sub-basal, basal and elevated concentrations and 2) hormonal and metabolic profiles in obese man. These studies will provide insight into hormonal regulation of glucose and amino acid flux, and serve as a basis for comparison with human diabetic syndromes.